Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome

Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajecto...
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Autor*in:	Priyanka D Abeyrathne [verfasserIn] Cha San Koh [verfasserIn] Timothy Grant [verfasserIn] Nikolaus Grigorieff [verfasserIn] Andrei A Korostelev [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Schlagwörter:	Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2

Übergeordnetes Werk:	In: eLife - eLife Sciences Publications Ltd, 2013, 5(2016)
Übergeordnetes Werk:	volume:5 ; year:2016

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.7554/eLife.14874

Katalog-ID:	DOAJ021105715

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520			\|a Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.
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allfields	10.7554/eLife.14874 doi (DE-627)DOAJ021105715 (DE-599)DOAJ092313fab65b4ba99f1e6a1f6dc57e6c DE-627 ger DE-627 rakwb eng QH301-705.5 Priyanka D Abeyrathne verfasserin aut Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation. Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2 Medicine R Science Q Biology (General) Cha San Koh verfasserin aut Timothy Grant verfasserin aut Nikolaus Grigorieff verfasserin aut Andrei A Korostelev verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 5(2016) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:5 year:2016 https://doi.org/10.7554/eLife.14874 kostenfrei https://doaj.org/article/092313fab65b4ba99f1e6a1f6dc57e6c kostenfrei https://elifesciences.org/articles/14874 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2016
spelling	10.7554/eLife.14874 doi (DE-627)DOAJ021105715 (DE-599)DOAJ092313fab65b4ba99f1e6a1f6dc57e6c DE-627 ger DE-627 rakwb eng QH301-705.5 Priyanka D Abeyrathne verfasserin aut Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation. Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2 Medicine R Science Q Biology (General) Cha San Koh verfasserin aut Timothy Grant verfasserin aut Nikolaus Grigorieff verfasserin aut Andrei A Korostelev verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 5(2016) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:5 year:2016 https://doi.org/10.7554/eLife.14874 kostenfrei https://doaj.org/article/092313fab65b4ba99f1e6a1f6dc57e6c kostenfrei https://elifesciences.org/articles/14874 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2016
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allfieldsSound	10.7554/eLife.14874 doi (DE-627)DOAJ021105715 (DE-599)DOAJ092313fab65b4ba99f1e6a1f6dc57e6c DE-627 ger DE-627 rakwb eng QH301-705.5 Priyanka D Abeyrathne verfasserin aut Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation. Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2 Medicine R Science Q Biology (General) Cha San Koh verfasserin aut Timothy Grant verfasserin aut Nikolaus Grigorieff verfasserin aut Andrei A Korostelev verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 5(2016) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:5 year:2016 https://doi.org/10.7554/eLife.14874 kostenfrei https://doaj.org/article/092313fab65b4ba99f1e6a1f6dc57e6c kostenfrei https://elifesciences.org/articles/14874 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2016
language	English
source	In eLife 5(2016) volume:5 year:2016
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institution	findex.gbv.de
topic_facet	Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2 Medicine R Science Q Biology (General)
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container_title	eLife
authorswithroles_txt_mv	Priyanka D Abeyrathne @@aut@@ Cha San Koh @@aut@@ Timothy Grant @@aut@@ Nikolaus Grigorieff @@aut@@ Andrei A Korostelev @@aut@@
publishDateDaySort_date	2016-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Priyanka D Abeyrathne
spellingShingle	Priyanka D Abeyrathne misc QH301-705.5 misc Taura syndrome virus misc ribosome misc internal ribosome entry site misc IRES misc translocation misc elongation factor eEF2 misc Medicine misc R misc Science misc Q misc Biology (General) Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
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topic_title	QH301-705.5 Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome Taura syndrome virus ribosome internal ribosome entry site IRES translocation elongation factor eEF2
topic	misc QH301-705.5 misc Taura syndrome virus misc ribosome misc internal ribosome entry site misc IRES misc translocation misc elongation factor eEF2 misc Medicine misc R misc Science misc Q misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc Taura syndrome virus misc ribosome misc internal ribosome entry site misc IRES misc translocation misc elongation factor eEF2 misc Medicine misc R misc Science misc Q misc Biology (General)
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title	Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
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title_full	Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
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title_sort	ensemble cryo-em uncovers inchworm-like translocation of a viral ires through the ribosome
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title_auth	Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
abstract	Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.
abstractGer	Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.
abstract_unstemmed	Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.
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title_short	Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome
url	https://doi.org/10.7554/eLife.14874 https://doaj.org/article/092313fab65b4ba99f1e6a1f6dc57e6c https://elifesciences.org/articles/14874 https://doaj.org/toc/2050-084X
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Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome

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