TY - JOUR
T1 - Decoupled side chain and backbone dynamics for proton translocation – M2 of influenza A
AU - Kalita, Monoj Mon
AU - Fischer, Wolfgang B.
N1 - Publisher Copyright:
© 2017, Springer-Verlag GmbH Germany.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - The 97 amino acid bitopic membrane protein M2 of influenza A forms a tetrameric bundle in which two of the monomers are covalently linked via a cysteine bridge. In its tetrameric assembly the protein conducts protons across the viral envelope and within intracellular compartments during the infectivity cycle of the virus. A key residue in the translocation of the protons is His-37 which forms a planar tetrad in the configuration of the bundle accepting and translocating the incoming protons from the N terminal side, exterior of the virus, to the C terminal side, inside the virus. With experimentally available data from NMR spectroscopy of the transmembrane domains of the tetrameric M2 bundle classical MD simulations are conducted with the protein bundle in different protonation stages in respect to His-37. A full correlation analysis (FCA) of the data sets with the His-37 tetrad either in a fully four times unprotonated or protonated state, assumed to mimic high and low pH in vivo, respectively, in both cases reveal asymmetric backbone dynamics. His-37 side chain rotation dynamics is increased at full protonation of the tetrad compared to the dynamics in the fully unprotonated state. The data suggest that proton translocation can be achieved by decoupled side chain or backbone dynamics. [Figure not available: see fulltext.].
AB - The 97 amino acid bitopic membrane protein M2 of influenza A forms a tetrameric bundle in which two of the monomers are covalently linked via a cysteine bridge. In its tetrameric assembly the protein conducts protons across the viral envelope and within intracellular compartments during the infectivity cycle of the virus. A key residue in the translocation of the protons is His-37 which forms a planar tetrad in the configuration of the bundle accepting and translocating the incoming protons from the N terminal side, exterior of the virus, to the C terminal side, inside the virus. With experimentally available data from NMR spectroscopy of the transmembrane domains of the tetrameric M2 bundle classical MD simulations are conducted with the protein bundle in different protonation stages in respect to His-37. A full correlation analysis (FCA) of the data sets with the His-37 tetrad either in a fully four times unprotonated or protonated state, assumed to mimic high and low pH in vivo, respectively, in both cases reveal asymmetric backbone dynamics. His-37 side chain rotation dynamics is increased at full protonation of the tetrad compared to the dynamics in the fully unprotonated state. The data suggest that proton translocation can be achieved by decoupled side chain or backbone dynamics. [Figure not available: see fulltext.].
KW - Full correlation analysis
KW - M2 of influenza A
KW - Molecular dynamics simulations
KW - NMR structure
KW - Protein dynamics
KW - Viral channel protein
UR - http://www.scopus.com/inward/record.url?scp=85021282410&partnerID=8YFLogxK
U2 - 10.1007/s00894-017-3389-6
DO - 10.1007/s00894-017-3389-6
M3 - Article
C2 - 28646429
AN - SCOPUS:85021282410
SN - 1610-2940
VL - 23
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 7
M1 - 212
ER -