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Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage
Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220004/ https://www.ncbi.nlm.nih.gov/pubmed/25240326 http://dx.doi.org/10.1016/j.virol.2014.08.023 |
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author | Steinberger, Jutta Grishkovskaya, Irina Cencic, Regina Juliano, Luiz Juliano, Maria A. Skern, Tim |
author_facet | Steinberger, Jutta Grishkovskaya, Irina Cencic, Regina Juliano, Luiz Juliano, Maria A. Skern, Tim |
author_sort | Steinberger, Jutta |
collection | PubMed |
description | Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave the cellular eukaryotic initiation factor (eIF) 4G. During infection, Lb(pro) removes six residues from its own C-terminus, generating sLb(pro). We present the structure of sLb(pro) bound to the inhibitor E64-R-P-NH(2), illustrating how sLb(pro) can cleave between Lys/Gly and Gly/Arg pairs. In intermolecular cleavage on polyprotein substrates, Lb(pro) was unaffected by P1 or P1′ substitutions and processed a substrate containing nine eIF4GI cleavage site residues whereas sLb(pro) failed to cleave the eIF4GI containing substrate and cleaved appreciably more slowly on mutated substrates. Introduction of 70 eIF4GI residues bearing the Lb(pro) binding site restored cleavage. These data imply that Lb(pro) and sLb(pro) may have different functions in infected cells. |
format | Online Article Text |
id | pubmed-4220004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42200042014-11-06 Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage Steinberger, Jutta Grishkovskaya, Irina Cencic, Regina Juliano, Luiz Juliano, Maria A. Skern, Tim Virology Article Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave the cellular eukaryotic initiation factor (eIF) 4G. During infection, Lb(pro) removes six residues from its own C-terminus, generating sLb(pro). We present the structure of sLb(pro) bound to the inhibitor E64-R-P-NH(2), illustrating how sLb(pro) can cleave between Lys/Gly and Gly/Arg pairs. In intermolecular cleavage on polyprotein substrates, Lb(pro) was unaffected by P1 or P1′ substitutions and processed a substrate containing nine eIF4GI cleavage site residues whereas sLb(pro) failed to cleave the eIF4GI containing substrate and cleaved appreciably more slowly on mutated substrates. Introduction of 70 eIF4GI residues bearing the Lb(pro) binding site restored cleavage. These data imply that Lb(pro) and sLb(pro) may have different functions in infected cells. Academic Press 2014-11 /pmc/articles/PMC4220004/ /pubmed/25240326 http://dx.doi.org/10.1016/j.virol.2014.08.023 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Article Steinberger, Jutta Grishkovskaya, Irina Cencic, Regina Juliano, Luiz Juliano, Maria A. Skern, Tim Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title | Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title_full | Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title_fullStr | Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title_full_unstemmed | Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title_short | Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage |
title_sort | foot-and-mouth disease virus leader proteinase: structural insights into the mechanism of intermolecular cleavage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220004/ https://www.ncbi.nlm.nih.gov/pubmed/25240326 http://dx.doi.org/10.1016/j.virol.2014.08.023 |
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