Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.

Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a...

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Autores principales: Etienne Decroly, Claire Debarnot, François Ferron, Mickael Bouvet, Bruno Coutard, Isabelle Imbert, Laure Gluais, Nicolas Papageorgiou, Andrew Sharff, Gérard Bricogne, Miguel Ortiz-Lombardia, Julien Lescar, Bruno Canard
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:5ede7db0af914726a3936efe63df46f12021-11-18T06:03:21ZCrystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.1553-73661553-737410.1371/journal.ppat.1002059https://doaj.org/article/5ede7db0af914726a3936efe63df46f12011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637813/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2'-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Ų surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in +RNA viruses.Etienne DecrolyClaire DebarnotFrançois FerronMickael BouvetBruno CoutardIsabelle ImbertLaure GluaisNicolas PapageorgiouAndrew SharffGérard BricogneMiguel Ortiz-LombardiaJulien LescarBruno CanardPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 5, p e1002059 (2011)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Etienne Decroly
Claire Debarnot
François Ferron
Mickael Bouvet
Bruno Coutard
Isabelle Imbert
Laure Gluais
Nicolas Papageorgiou
Andrew Sharff
Gérard Bricogne
Miguel Ortiz-Lombardia
Julien Lescar
Bruno Canard
Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
description Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2'-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Ų surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in +RNA viruses.
format article
author Etienne Decroly
Claire Debarnot
François Ferron
Mickael Bouvet
Bruno Coutard
Isabelle Imbert
Laure Gluais
Nicolas Papageorgiou
Andrew Sharff
Gérard Bricogne
Miguel Ortiz-Lombardia
Julien Lescar
Bruno Canard
author_facet Etienne Decroly
Claire Debarnot
François Ferron
Mickael Bouvet
Bruno Coutard
Isabelle Imbert
Laure Gluais
Nicolas Papageorgiou
Andrew Sharff
Gérard Bricogne
Miguel Ortiz-Lombardia
Julien Lescar
Bruno Canard
author_sort Etienne Decroly
title Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
title_short Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
title_full Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
title_fullStr Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
title_full_unstemmed Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
title_sort crystal structure and functional analysis of the sars-coronavirus rna cap 2'-o-methyltransferase nsp10/nsp16 complex.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/5ede7db0af914726a3936efe63df46f1
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