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dc.contributor.authorKerry, Philip S.
dc.contributor.authorAyllon, Juan
dc.contributor.authorTaylor, Margaret A.
dc.contributor.authorHass, Claudia
dc.contributor.authorLewis, Andrew
dc.contributor.authorGarcia-Sastre, Adolfo
dc.contributor.authorRandall, Richard E.
dc.contributor.authorHale, Benjamin G.
dc.contributor.authorRussell, Rupert J.
dc.identifier.citationKerry , 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 .
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427017
dc.descriptionWork in St. Andrews was supported by the Medical Research Council, UK (RER and RJR), and the Scottish Funding Council (RJR).en
dc.description.abstractInfluenza 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.relation.ispartofPLoS Oneen
dc.subjectNonstructural protein-1en
dc.subjectStructural basisen
dc.subjectBinding motifen
dc.subjectQR355 Virologyen
dc.titleA transient homotypic interaction model for the influenza A virus NS1 protein effector domainen
dc.typeJournal articleen
dc.contributor.sponsorMedical Research Councilen
dc.contributor.sponsorMedical Research Councilen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. University of St Andrewsen
dc.contributor.institutionUniversity of St Andrews. School of Physics and Astronomyen
dc.description.statusPeer revieweden

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