3O9R

Effector domain of NS1 from influenza A/PR/8/34 containing a W187A mutation

Summary for 3O9R

• Entry DOI: 10.2210/pdb3o9r/pdb
• Related: 3O9Q 3O9S 3O9T 3O9U 3OA9
• Descriptor: Nonstructural protein 1 (2 entities in total)
• Functional Keywords: viral protein
• Biological source: Influenza A virus (A/reassortant/IVR108(Sydney/5/1995 x Puerto Rico/8/1934)(H3N2))
• Total number of polymer chains: 2
• Total formula weight: 33751.01

Authors

Kerry, P.S.,Lewis, A.,Hale, B.G.,Hass, C.,Taylor, M.A.,Randall, R.E.,Russell, R.J.M. (deposition date: 2010-08-04, release date: 2011-05-11, Last modification date: 2024-02-21)

Primary 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.
A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain.
Plos One, 6:e17946-e17946, 2011

PubMed 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.

PubMed: 21464929
DOI: 10.1371/journal.pone.0017946

Experimental method

X-RAY DIFFRACTION (2 Å)