2026-11-03T02:58:40Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/79972023-11-23T12:25:34Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863
Repositorio Institucional de la Universidad de Burgos
author
Kerry, Philip S.
author
Ayllón Barasoain, Juan
author
Taylor, Margaret A.
author
Hass, Claudia
author
Lewis, Andrew
author
García Sastre, Adolfo
author
Randall, Richard E.
author
Hale, Benjamin G.
author
Russell, Rupert J.
2023-11-13T08:06:30Z
2023-11-13T08:06:30Z
2011
http://hdl.handle.net/10259/7997
10.1371/journal.pone.0017946
1932-6203
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.
eng
Atribución 4.0 Internacional
A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain
info:eu-repo/semantics/article
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URL
https://riubu.ubu.es/bitstream/10259/7997/1/Kerry-PlosOne_2011.pdf
File
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56e381ae3c7bed22c52055e24e1205e2
1070635
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Kerry-PlosOne_2011.pdf