Exploring the repeat protein universe through computational protein design

A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in mo...
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Autor*in:	T J Brunette [verfasserIn] Fabio Parmeggiani Po-Ssu Huang Gira Bhabha Damian C Ekiert Susan E Tsutakawa Greg L Hura John A Tainer David Baker

Format:	Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure

Übergeordnetes Werk:	Enthalten in: Nature - London : Macmillan Publishers Limited, part of Springer Nature, 1869, 528(2015), 7583, Seite 580-584
Übergeordnetes Werk:	volume:528 ; year:2015 ; number:7583 ; pages:580-584

Links:	Volltext Link aufrufen Link aufrufen

DOI / URN:	10.1038/nature16162

Katalog-ID:	OLC1969636793

Internformat


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520			\|a A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
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publishDate	2015
allfields	10.1038/nature16162 doi PQ20160430 (DE-627)OLC1969636793 (DE-599)GBVOLC1969636793 (PRQ)c2719-44d521ca4b2344980576f9805079069405d134f840f0a923722765185ffefcd70 (KEY)0072945020150000528758300580exploringtherepeatproteinuniversethroughcomputatio DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid T J Brunette verfasserin aut Exploring the repeat protein universe through computational protein design 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure Fabio Parmeggiani oth Po-Ssu Huang oth Gira Bhabha oth Damian C Ekiert oth Susan E Tsutakawa oth Greg L Hura oth John A Tainer oth David Baker oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 528(2015), 7583, Seite 580-584 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:528 year:2015 number:7583 pages:580-584 http://dx.doi.org/10.1038/nature16162 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 528 2015 7583 580-584
spelling	10.1038/nature16162 doi PQ20160430 (DE-627)OLC1969636793 (DE-599)GBVOLC1969636793 (PRQ)c2719-44d521ca4b2344980576f9805079069405d134f840f0a923722765185ffefcd70 (KEY)0072945020150000528758300580exploringtherepeatproteinuniversethroughcomputatio DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid T J Brunette verfasserin aut Exploring the repeat protein universe through computational protein design 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure Fabio Parmeggiani oth Po-Ssu Huang oth Gira Bhabha oth Damian C Ekiert oth Susan E Tsutakawa oth Greg L Hura oth John A Tainer oth David Baker oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 528(2015), 7583, Seite 580-584 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:528 year:2015 number:7583 pages:580-584 http://dx.doi.org/10.1038/nature16162 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 528 2015 7583 580-584
allfields_unstemmed	10.1038/nature16162 doi PQ20160430 (DE-627)OLC1969636793 (DE-599)GBVOLC1969636793 (PRQ)c2719-44d521ca4b2344980576f9805079069405d134f840f0a923722765185ffefcd70 (KEY)0072945020150000528758300580exploringtherepeatproteinuniversethroughcomputatio DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid T J Brunette verfasserin aut Exploring the repeat protein universe through computational protein design 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure Fabio Parmeggiani oth Po-Ssu Huang oth Gira Bhabha oth Damian C Ekiert oth Susan E Tsutakawa oth Greg L Hura oth John A Tainer oth David Baker oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 528(2015), 7583, Seite 580-584 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:528 year:2015 number:7583 pages:580-584 http://dx.doi.org/10.1038/nature16162 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 528 2015 7583 580-584
allfieldsGer	10.1038/nature16162 doi PQ20160430 (DE-627)OLC1969636793 (DE-599)GBVOLC1969636793 (PRQ)c2719-44d521ca4b2344980576f9805079069405d134f840f0a923722765185ffefcd70 (KEY)0072945020150000528758300580exploringtherepeatproteinuniversethroughcomputatio DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid T J Brunette verfasserin aut Exploring the repeat protein universe through computational protein design 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure Fabio Parmeggiani oth Po-Ssu Huang oth Gira Bhabha oth Damian C Ekiert oth Susan E Tsutakawa oth Greg L Hura oth John A Tainer oth David Baker oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 528(2015), 7583, Seite 580-584 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:528 year:2015 number:7583 pages:580-584 http://dx.doi.org/10.1038/nature16162 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 528 2015 7583 580-584
allfieldsSound	10.1038/nature16162 doi PQ20160430 (DE-627)OLC1969636793 (DE-599)GBVOLC1969636793 (PRQ)c2719-44d521ca4b2344980576f9805079069405d134f840f0a923722765185ffefcd70 (KEY)0072945020150000528758300580exploringtherepeatproteinuniversethroughcomputatio DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid T J Brunette verfasserin aut Exploring the repeat protein universe through computational protein design 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering. Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure Fabio Parmeggiani oth Po-Ssu Huang oth Gira Bhabha oth Damian C Ekiert oth Susan E Tsutakawa oth Greg L Hura oth John A Tainer oth David Baker oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 528(2015), 7583, Seite 580-584 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:528 year:2015 number:7583 pages:580-584 http://dx.doi.org/10.1038/nature16162 Volltext http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 528 2015 7583 580-584
language	English
source	Enthalten in Nature 528(2015), 7583, Seite 580-584 volume:528 year:2015 number:7583 pages:580-584
sourceStr	Enthalten in Nature 528(2015), 7583, Seite 580-584 volume:528 year:2015 number:7583 pages:580-584
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure
dewey-raw	070
isfreeaccess_bool	false
container_title	Nature
authorswithroles_txt_mv	T J Brunette @@aut@@ Fabio Parmeggiani @@oth@@ Po-Ssu Huang @@oth@@ Gira Bhabha @@oth@@ Damian C Ekiert @@oth@@ Susan E Tsutakawa @@oth@@ Greg L Hura @@oth@@ John A Tainer @@oth@@ David Baker @@oth@@
publishDateDaySort_date	2015-01-01T00:00:00Z
hierarchy_top_id	129292834
dewey-sort	270
id	OLC1969636793
language_de	englisch
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author	T J Brunette
spellingShingle	T J Brunette ddc 070 ddc 500 fid BIODIV misc Molecular structure misc Proteins misc Molecular biology misc Amino acids misc Polypeptides misc Proteins - chemistry misc Leucine misc Dosage and administration misc Helix-loop-helix motif misc Research misc Crystals misc Structure Exploring the repeat protein universe through computational protein design
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topic_title	070 500 DNB 500 AVZ BIODIV fid Exploring the repeat protein universe through computational protein design Molecular structure Proteins Molecular biology Amino acids Polypeptides Proteins - chemistry Leucine Dosage and administration Helix-loop-helix motif Research Crystals Structure
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title	Exploring the repeat protein universe through computational protein design
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title_full	Exploring the repeat protein universe through computational protein design
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title_sort	exploring the repeat protein universe through computational protein design
title_auth	Exploring the repeat protein universe through computational protein design
abstract	A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
abstractGer	A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
abstract_unstemmed	A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
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container_issue	7583
title_short	Exploring the repeat protein universe through computational protein design
url	http://dx.doi.org/10.1038/nature16162 http://www.ncbi.nlm.nih.gov/pubmed/26675729 http://search.proquest.com/docview/1752192051
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author2	Fabio Parmeggiani Po-Ssu Huang Gira Bhabha Damian C Ekiert Susan E Tsutakawa Greg L Hura John A Tainer David Baker
author2Str	Fabio Parmeggiani Po-Ssu Huang Gira Bhabha Damian C Ekiert Susan E Tsutakawa Greg L Hura John A Tainer David Baker
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Exploring the repeat protein universe through computational protein design

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