Structural rearrangement of the influenza polymerase PB2 C-ter domainupon importin binding: explaining nuclear import and host adaptation

DOI

Influenza A is a major concern for human health as it causes important seasonal epidemics. Also, through mechanisms of genetic drift and reassortment, very lethal influenza viruses emerge sporadically, causing devastating pandemics such as the 1918 Spanish flu which caused over 50 million deaths. Interspecies adaptation of influenza requires temperature adaptation to the host, which occurs mainly through mutation of the polymerase, notably in the C-terminal "627-NLS"; domain of the PB2 subunit. Although the crystallographic structure of 627-NLS has been solved and nM binding to importin alpha measured, it is unclear how this interaction can occur because simple docking with importin alpha structures predicts large steric clashes. Thus, another conformation of 627-NLS must exist in solution this interaction to occur. Using SAXS and NMR, I have shown that a completely different open conformation of 627-NLS exists in solution and this may explain how it binds importin alpha. Our aim is to better characterize this open conformation of the 627-NLS, using SANS contrast variation to get a low resolution description of each component in the context of the complex.

Identifier
DOI https://doi.org/10.5291/ILL-DATA.8-03-825
Metadata Access https://data.ill.fr/openaire/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=10.5291/ILL-DATA.8-03-825
Provenance
Creator Martel, Anne; Hart, Darren; Delaforge, Elise; Jensen, Malene Ringkjobing; Blackledge, Martin
Publisher Institut Laue-Langevin
Publication Year 2015
Rights OpenAccess; info:eu-repo/semantics/openAccess
OpenAccess true
Representation
Resource Type Dataset
Size 310 MB
Version 1
Discipline Particles, Nuclei and Fields