title: Structural analysis of influenza A virus matrix protein M1 and its self-assemblies at low pH.
abstract: Influenza A virus matrix protein M1 is one of the most important and abundant proteins in the virus particles broadly involved in essential processes of the viral life cycle. The absence of high-resolution data on the full-length M1 makes the structural investigation of the intact protein particularly important. We employed synchrotron small-angle X-ray scattering (SAXS), analytical ultracentrifugation and atomic force microscopy (AFM) to study the structure of M1 at acidic pH. The low-resolution structural models built from the SAXS data reveal a structurally anisotropic M1 molecule consisting of a compact NM-fragment and an extended and partially flexible C-terminal domain. The M1 monomers co-exist in solution with a small fraction of large clusters that have a layered architecture similar to that observed in the authentic influenza virions. AFM analysis on a lipid-like negatively charged surface reveals that M1 forms ordered stripes correlating well with the clusters observed by SAXS. The free NM-domain is monomeric in acidic solution with the overall structure similar to that observed in previously determined crystal structures. The NM-domain does not spontaneously self assemble supporting the key role of the C-terminus of M1 in the formation of supramolecular structures. Our results suggest that the flexibility of the C-terminus is an essential feature, which may be responsible for the multi-functionality of the entire protein. In particular, this flexibility could allow M1 to structurally organise the viral membrane to maintain the integrity and the shape of the intact influenza virus.
authors.affiliation: Shubnikov Institute of Crystallography, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Eleonora V
authors.initials: EV
authors.lastname: Shtykova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Lyudmila A
authors.initials: LA
authors.lastname: Baratova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Fedorova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Radyukhin
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Ksenofontov
authors.affiliation: Shubnikov Institute of Crystallography, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Volkov
authors.affiliation: Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Shishkov
authors.affiliation: Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Dolgov
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russia ; Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Liudmila A
authors.initials: LA
authors.lastname: Shilova
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russia ; Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Batishchev
authors.affiliation: EMBL, Hamburg Outstation, c/o DESY, Hamburg, Germany.
authors.forename: Cy M
authors.initials: CM
authors.lastname: Jeffries
authors.affiliation: EMBL, Hamburg Outstation, c/o DESY, Hamburg, Germany.
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
mesh_terms: D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D011487:Protein Conformation; D053838:Scattering, Small Angle; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins