Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyro...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kruusvee, Valdeko [verfasserIn] J. Lyst, Matthew Taylor, Ceitidh Tarnauskaite, Zygimante P. Bird, Adrian G. Cook, Atlanta

Format:	Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein

Übergeordnetes Werk:	Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 114(2017), 16, Seite E3243
Übergeordnetes Werk:	volume:114 ; year:2017 ; number:16 ; pages:E3243

Links:	Volltext Link aufrufen

DOI / URN:	10.1073/pnas.1700731114

Katalog-ID:	OLC1995551201

Internformat


LEADER	01000caa a2200265 4500
001	OLC1995551201
003	DE-627
005	20230715062521.0
007	tu
008	170721s2017 xx \|\|\|\|\| 00\| \|\|eng c
024	7		\|a 10.1073/pnas.1700731114 \|2 doi
028	5	2	\|a PQ20170901
035			\|a (DE-627)OLC1995551201
035			\|a (DE-599)GBVOLC1995551201
035			\|a (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190
035			\|a (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
082	0	4	\|a 500 \|q DE-101
082	0	4	\|a 570 \|q AVZ
084			\|a LING \|2 fid
084			\|a BIODIV \|2 fid
100	1		\|a Kruusvee, Valdeko \|e verfasserin \|4 aut
245	1	0	\|a Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
264		1	\|c 2017
336			\|a Text \|b txt \|2 rdacontent
337			\|a ohne Hilfsmittel zu benutzen \|b n \|2 rdamedia
338			\|a Band \|b nc \|2 rdacarrier
520			\|a Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.
650		4	\|a Rett syndrome
650		4	\|a Health aspects
650		4	\|a Gene mutations
650		4	\|a Genetic aspects
650		4	\|a Neurological disorders
650		4	\|a Missense mutation
650		4	\|a In vitro testing
650		4	\|a Transducin
650		4	\|a Residues
650		4	\|a Retinoic acid
650		4	\|a Mutations
650		4	\|a Thyroid
650		4	\|a Brain
650		4	\|a Receptors
650		4	\|a Molecules
650		4	\|a CpG islands
650		4	\|a Disorders
650		4	\|a Methyl-CpG binding protein
650		4	\|a Genes
650		4	\|a SMRT protein
650		4	\|a DNA
650		4	\|a Binding sites
650		4	\|a Proteins
650		4	\|a Deoxyribonucleic acid
650		4	\|a Binding
650		4	\|a Mutation
650		4	\|a MeCP2 protein
700	1		\|a J. Lyst, Matthew \|4 oth
700	1		\|a Taylor, Ceitidh \|4 oth
700	1		\|a Tarnauskaite, Zygimante \|4 oth
700	1		\|a P. Bird, Adrian \|4 oth
700	1		\|a G. Cook, Atlanta \|4 oth
773	0	8	\|i Enthalten in \|t Proceedings of the National Academy of Sciences of the United States of America \|d Washington, DC : NAS, 1877 \|g 114(2017), 16, Seite E3243 \|w (DE-627)129505269 \|w (DE-600)209104-5 \|w (DE-576)014909189 \|x 0027-8424 \|7 nnns
773	1	8	\|g volume:114 \|g year:2017 \|g number:16 \|g pages:E3243
856	4	1	\|u http://dx.doi.org/10.1073/pnas.1700731114 \|3 Volltext
856	4	2	\|u https://search.proquest.com/docview/1897794112
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_OLC
912			\|a FID-LING
912			\|a FID-BIODIV
912			\|a SSG-OLC-PHY
912			\|a SSG-OLC-CHE
912			\|a SSG-OLC-MAT
912			\|a SSG-OLC-FOR
912			\|a SSG-OLC-PHA
912			\|a SSG-OLC-DE-84
912			\|a SSG-OPC-MAT
912			\|a SSG-OPC-FOR
912			\|a GBV_ILN_40
912			\|a GBV_ILN_59
951			\|a AR
952			\|d 114 \|j 2017 \|e 16 \|h E3243

Indexfelder

author_variant	v k vk
matchkey_str	article:00278424:2017----::tutroteeptl1opervasmlclraifrety
hierarchy_sort_str	2017
publishDate	2017
allfields	10.1073/pnas.1700731114 doi PQ20170901 (DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Kruusvee, Valdeko verfasserin aut Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function. Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein J. Lyst, Matthew oth Taylor, Ceitidh oth Tarnauskaite, Zygimante oth P. Bird, Adrian oth G. Cook, Atlanta oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 16, Seite E3243 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:16 pages:E3243 http://dx.doi.org/10.1073/pnas.1700731114 Volltext https://search.proquest.com/docview/1897794112 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 16 E3243
spelling	10.1073/pnas.1700731114 doi PQ20170901 (DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Kruusvee, Valdeko verfasserin aut Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function. Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein J. Lyst, Matthew oth Taylor, Ceitidh oth Tarnauskaite, Zygimante oth P. Bird, Adrian oth G. Cook, Atlanta oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 16, Seite E3243 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:16 pages:E3243 http://dx.doi.org/10.1073/pnas.1700731114 Volltext https://search.proquest.com/docview/1897794112 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 16 E3243
allfields_unstemmed	10.1073/pnas.1700731114 doi PQ20170901 (DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Kruusvee, Valdeko verfasserin aut Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function. Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein J. Lyst, Matthew oth Taylor, Ceitidh oth Tarnauskaite, Zygimante oth P. Bird, Adrian oth G. Cook, Atlanta oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 16, Seite E3243 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:16 pages:E3243 http://dx.doi.org/10.1073/pnas.1700731114 Volltext https://search.proquest.com/docview/1897794112 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 16 E3243
allfieldsGer	10.1073/pnas.1700731114 doi PQ20170901 (DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Kruusvee, Valdeko verfasserin aut Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function. Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein J. Lyst, Matthew oth Taylor, Ceitidh oth Tarnauskaite, Zygimante oth P. Bird, Adrian oth G. Cook, Atlanta oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 16, Seite E3243 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:16 pages:E3243 http://dx.doi.org/10.1073/pnas.1700731114 Volltext https://search.proquest.com/docview/1897794112 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 16 E3243
allfieldsSound	10.1073/pnas.1700731114 doi PQ20170901 (DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Kruusvee, Valdeko verfasserin aut Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function. Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein J. Lyst, Matthew oth Taylor, Ceitidh oth Tarnauskaite, Zygimante oth P. Bird, Adrian oth G. Cook, Atlanta oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 16, Seite E3243 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:16 pages:E3243 http://dx.doi.org/10.1073/pnas.1700731114 Volltext https://search.proquest.com/docview/1897794112 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 16 E3243
language	English
source	Enthalten in Proceedings of the National Academy of Sciences of the United States of America 114(2017), 16, Seite E3243 volume:114 year:2017 number:16 pages:E3243
sourceStr	Enthalten in Proceedings of the National Academy of Sciences of the United States of America 114(2017), 16, Seite E3243 volume:114 year:2017 number:16 pages:E3243
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein
dewey-raw	500
isfreeaccess_bool	false
container_title	Proceedings of the National Academy of Sciences of the United States of America
authorswithroles_txt_mv	Kruusvee, Valdeko @@aut@@ J. Lyst, Matthew @@oth@@ Taylor, Ceitidh @@oth@@ Tarnauskaite, Zygimante @@oth@@ P. Bird, Adrian @@oth@@ G. Cook, Atlanta @@oth@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	129505269
dewey-sort	3500
id	OLC1995551201
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1995551201</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230715062521.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170721s2017 xx \|\|\|\|\| 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1700731114</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170901</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1995551201</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1995551201</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DE-101</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Kruusvee, Valdeko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rett syndrome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Health aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neurological disorders</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Missense mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">In vitro testing</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transducin</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Residues</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Retinoic acid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Thyroid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Receptors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Molecules</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CpG islands</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Disorders</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Methyl-CpG binding protein</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SMRT protein</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Binding sites</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proteins</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Binding</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">MeCP2 protein</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">J. Lyst, Matthew</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Taylor, Ceitidh</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tarnauskaite, Zygimante</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">P. Bird, Adrian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">G. Cook, Atlanta</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">114(2017), 16, Seite E3243</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:114</subfield><subfield code="g">year:2017</subfield><subfield code="g">number:16</subfield><subfield code="g">pages:E3243</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1700731114</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://search.proquest.com/docview/1897794112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">114</subfield><subfield code="j">2017</subfield><subfield code="e">16</subfield><subfield code="h">E3243</subfield></datafield></record></collection>
author	Kruusvee, Valdeko
spellingShingle	Kruusvee, Valdeko ddc 500 ddc 570 fid LING fid BIODIV misc Rett syndrome misc Health aspects misc Gene mutations misc Genetic aspects misc Neurological disorders misc Missense mutation misc In vitro testing misc Transducin misc Residues misc Retinoic acid misc Mutations misc Thyroid misc Brain misc Receptors misc Molecules misc CpG islands misc Disorders misc Methyl-CpG binding protein misc Genes misc SMRT protein misc DNA misc Binding sites misc Proteins misc Deoxyribonucleic acid misc Binding misc Mutation misc MeCP2 protein Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
authorStr	Kruusvee, Valdeko
ppnlink_with_tag_str_mv	@@773@@(DE-627)129505269
format	Article
dewey-ones	500 - Natural sciences & mathematics 570 - Life sciences; biology
delete_txt_mv	keep
author_role	aut
collection	OLC
remote_str	false
illustrated	Not Illustrated
issn	0027-8424
topic_title	500 DE-101 570 AVZ LING fid BIODIV fid Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders Rett syndrome Health aspects Gene mutations Genetic aspects Neurological disorders Missense mutation In vitro testing Transducin Residues Retinoic acid Mutations Thyroid Brain Receptors Molecules CpG islands Disorders Methyl-CpG binding protein Genes SMRT protein DNA Binding sites Proteins Deoxyribonucleic acid Binding Mutation MeCP2 protein
topic	ddc 500 ddc 570 fid LING fid BIODIV misc Rett syndrome misc Health aspects misc Gene mutations misc Genetic aspects misc Neurological disorders misc Missense mutation misc In vitro testing misc Transducin misc Residues misc Retinoic acid misc Mutations misc Thyroid misc Brain misc Receptors misc Molecules misc CpG islands misc Disorders misc Methyl-CpG binding protein misc Genes misc SMRT protein misc DNA misc Binding sites misc Proteins misc Deoxyribonucleic acid misc Binding misc Mutation misc MeCP2 protein
topic_unstemmed	ddc 500 ddc 570 fid LING fid BIODIV misc Rett syndrome misc Health aspects misc Gene mutations misc Genetic aspects misc Neurological disorders misc Missense mutation misc In vitro testing misc Transducin misc Residues misc Retinoic acid misc Mutations misc Thyroid misc Brain misc Receptors misc Molecules misc CpG islands misc Disorders misc Methyl-CpG binding protein misc Genes misc SMRT protein misc DNA misc Binding sites misc Proteins misc Deoxyribonucleic acid misc Binding misc Mutation misc MeCP2 protein
topic_browse	ddc 500 ddc 570 fid LING fid BIODIV misc Rett syndrome misc Health aspects misc Gene mutations misc Genetic aspects misc Neurological disorders misc Missense mutation misc In vitro testing misc Transducin misc Residues misc Retinoic acid misc Mutations misc Thyroid misc Brain misc Receptors misc Molecules misc CpG islands misc Disorders misc Methyl-CpG binding protein misc Genes misc SMRT protein misc DNA misc Binding sites misc Proteins misc Deoxyribonucleic acid misc Binding misc Mutation misc MeCP2 protein
format_facet	Aufsätze Gedruckte Aufsätze
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	nc
author2_variant	l m j lm lmj c t ct z t zt b a p ba bap c a g ca cag
hierarchy_parent_title	Proceedings of the National Academy of Sciences of the United States of America
hierarchy_parent_id	129505269
dewey-tens	500 - Science 570 - Life sciences; biology
hierarchy_top_title	Proceedings of the National Academy of Sciences of the United States of America
isfreeaccess_txt	false
familylinks_str_mv	(DE-627)129505269 (DE-600)209104-5 (DE-576)014909189
title	Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
ctrlnum	(DE-627)OLC1995551201 (DE-599)GBVOLC1995551201 (PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190 (KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba
title_full	Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
author_sort	Kruusvee, Valdeko
journal	Proceedings of the National Academy of Sciences of the United States of America
journalStr	Proceedings of the National Academy of Sciences of the United States of America
lang_code	eng
isOA_bool	false
dewey-hundreds	500 - Science
recordtype	marc
publishDateSort	2017
contenttype_str_mv	txt
author_browse	Kruusvee, Valdeko
container_volume	114
class	500 DE-101 570 AVZ LING fid BIODIV fid
format_se	Aufsätze
author-letter	Kruusvee, Valdeko
doi_str_mv	10.1073/pnas.1700731114
dewey-full	500 570
title_sort	structure of the mecp2-tblr1 complex reveals a molecular basis for rett syndrome and related disorders
title_auth	Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
abstract	Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.
abstractGer	Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.
abstract_unstemmed	Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59
container_issue	16
title_short	Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders
url	http://dx.doi.org/10.1073/pnas.1700731114 https://search.proquest.com/docview/1897794112
remote_bool	false
author2	J. Lyst, Matthew Taylor, Ceitidh Tarnauskaite, Zygimante P. Bird, Adrian G. Cook, Atlanta
author2Str	J. Lyst, Matthew Taylor, Ceitidh Tarnauskaite, Zygimante P. Bird, Adrian G. Cook, Atlanta
ppnlink	129505269
mediatype_str_mv	n
isOA_txt	false
hochschulschrift_bool	false
author2_role	oth oth oth oth oth
doi_str	10.1073/pnas.1700731114
up_date	2024-07-03T22:09:44.641Z
_version_	1803597470385569792
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1995551201</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230715062521.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170721s2017 xx \|\|\|\|\| 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1700731114</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170901</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1995551201</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1995551201</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)g1163-dd6d0c93c8d19a0534300e2ee60b745f18ea5527f1afaf54410ea91bf314cd190</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920170000114001603243structureofthemecp2tblr1complexrevealsamolecularba</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DE-101</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Kruusvee, Valdeko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rett syndrome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Health aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neurological disorders</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Missense mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">In vitro testing</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transducin</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Residues</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Retinoic acid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Thyroid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brain</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Receptors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Molecules</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CpG islands</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Disorders</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Methyl-CpG binding protein</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SMRT protein</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Binding sites</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proteins</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Binding</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">MeCP2 protein</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">J. Lyst, Matthew</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Taylor, Ceitidh</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tarnauskaite, Zygimante</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">P. Bird, Adrian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">G. Cook, Atlanta</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">114(2017), 16, Seite E3243</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:114</subfield><subfield code="g">year:2017</subfield><subfield code="g">number:16</subfield><subfield code="g">pages:E3243</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1700731114</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://search.proquest.com/docview/1897794112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">114</subfield><subfield code="j">2017</subfield><subfield code="e">16</subfield><subfield code="h">E3243</subfield></datafield></record></collection>
score	7.3994207

Nicht das Richtige dabei?

Schreiben Sie uns!

Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?