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A transient homotypic interaction model for the influenza A virus NS1 protein effector domain
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dc.contributor.author | Kerry, Philip S. | |
dc.contributor.author | Ayllon, Juan | |
dc.contributor.author | Taylor, Margaret A. | |
dc.contributor.author | Hass, Claudia | |
dc.contributor.author | Lewis, Andrew | |
dc.contributor.author | Garcia-Sastre, Adolfo | |
dc.contributor.author | Randall, Richard E. | |
dc.contributor.author | Hale, Benjamin G. | |
dc.contributor.author | Russell, Rupert J. | |
dc.date.accessioned | 2012-01-20T10:31:03Z | |
dc.date.available | 2012-01-20T10:31:03Z | |
dc.date.issued | 2011-03-28 | |
dc.identifier.citation | Kerry , P S , Ayllon , J , Taylor , M A , Hass , C , Lewis , A , Garcia-Sastre , A , Randall , R E , Hale , B G & Russell , R J 2011 , ' A transient homotypic interaction model for the influenza A virus NS1 protein effector domain ' , PLoS One , vol. 6 , no. 3 , e17946 . https://doi.org/10.1371/journal.pone.0017946 | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | PURE: 16587158 | |
dc.identifier.other | PURE UUID: c3370564-86ef-4427-90d7-c3374bcea4b6 | |
dc.identifier.other | WOS: 000289053800008 | |
dc.identifier.other | Scopus: 79953159555 | |
dc.identifier.other | ORCID: /0000-0002-9304-6678/work/60427017 | |
dc.identifier.uri | https://hdl.handle.net/10023/2177 | |
dc.description | Work in St. Andrews was supported by the Medical Research Council, UK (RER and RJR), and the Scottish Funding Council (RJR). | en |
dc.description.abstract | Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins. | |
dc.format.extent | 13 | |
dc.language.iso | eng | |
dc.relation.ispartof | PLoS One | en |
dc.rights | © 2011 Kerry et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en |
dc.subject | Double-stranded-rna | en |
dc.subject | X-ray-structure | en |
dc.subject | Nonstructural protein-1 | en |
dc.subject | Iinfected-cells | en |
dc.subject | Structural basis | en |
dc.subject | Binding motif | en |
dc.subject | Interferon | en |
dc.subject | Activation | en |
dc.subject | Dimerization | en |
dc.subject | Recognition | en |
dc.subject | QR355 Virology | en |
dc.subject.lcc | QR355 | en |
dc.title | A transient homotypic interaction model for the influenza A virus NS1 protein effector domain | en |
dc.type | Journal article | en |
dc.contributor.sponsor | Medical Research Council | en |
dc.contributor.sponsor | Medical Research Council | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. University of St Andrews | en |
dc.contributor.institution | University of St Andrews. School of Physics and Astronomy | en |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0017946 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | G0601126 | en |
dc.identifier.grantnumber | G0700805 | en |
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