SCIENTIFIC RepoRts | 7: 16793 | DOI:10.1038/s41598-017-16986-y
Inuenza virus Matrix Protein M1
preserves its conformation with
pH, changing multimerization
state at the priming stage due to
Eleonora V. Shtykova
, Liubov A. Dadinova
, Natalia V. Fedorova
, Andrey E. Golanikov
Elena N. Bogacheva
, Alexander L. Ksenofontov
, Liudmila A. Baratova
, Liudmila A.
, Vsevolod Yu. Tashkin
, Timur R. Galimzyanov
, Cy M. Jeries
, Dmitri I.
& Oleg V. Batishchev
Inuenza A virus matrix protein M1 plays an essential role in the virus lifecycle, but its functional
and structural properties are not entirely dened. Here we employed small-angle X-ray scattering,
atomic force microscopy and zeta-potential measurements to characterize the overall structure and
association behavior of the full-length M1 at dierent pH conditions. We demonstrate that the protein
consists of a globular N-terminal domain and a exible C-terminal extension. The globular N-terminal
domain of M1 monomers appears preserved in the range of pH from 4.0 to 6.8, while the C-terminal
domain remains exible and the tendency to form multimers changes dramatically. We found that
the protein multimerization process is reversible, whereby the binding between M1 molecules starts
to break around pH 6. A predicted electrostatic model of M1 self-assembly at dierent pH revealed a
good agreement with zeta-potential measurements, allowing one to assess the role of M1 domains in
M1-M1 and M1-lipid interactions. Together with the protein sequence analysis, these results provide
insights into the mechanism of M1 scaold formation and the major role of the exible and disordered
C-terminal domain in this process.
Inuenza viruses belongs to the most widespread and potentially dangerous pathogenic group of viruses in the
. Inuenza A is an enveloped virus belonging the Orthomixoviridae family
. Its outer envelope is formed
by host cell derived bilayer lipid membrane, BLM, containing incorporated glycoproteins haemagglutinin (HA)
and neuraminidase (NA) along with the proton channel M2. e inner shell of the virion is represented by a
membrane-associated scaold of matrix proteins, M1, that makes contacts with both viral ribonucleoproteins,
RNP, and lipid envelope with the cytoplasmic tails of HA and NA
. Inuenza virus penetrates the cell using pre-
dominantly endocytosic pathway
, resulting in the virion entering into the endosome. A pH drop inside the late
endosome triggers the fusion of the viral and endosomal membranes
. Under these conditions, the rst step is a
at a pH of around 6.0 that causes a possible conformational change in M1 protein and the subse-
quent dissociation from the viral RNP
resulting in a loss of viral particle rigidity
. During this process, M1-lipid
interactions remain intact
. A conformational change in HA at pH 5.5 leads to a tight contact of the viral and
endosomal membranes and formation of the small fusion pore
. Freezing of the system at the given pH value
reveals no change in the viral envelope and only the target membrane is deformed under action of viral fusion
Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics”
of Russian Academy of Sciences, Moscow, Russia.
Semenov Institute of Chemical Physics, Russian Academy of
Sciences, Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow,
Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology, Dolgoprudniy, Russia.
National University of Science and Technology
“MISiS”, Moscow, Russia.
European Molecular Biology Laboratory, Hamburg Outstation, c/o DESY, Hamburg,
Germany. Correspondence and requests for materials should be addressed to O.V.B. (email: email@example.com)
Received: 8 August 2017
Accepted: 21 November 2017
Published: xx xx xxxx