Ab initio calculations and validation of the pH-dependent structures of the His37-Trp41 quartet, the heart of acid activation and proton conductance in the M2 protein of Influenza A virus.

ABSTRACT: The M2 protein of Influenza A virus forms a homotetrameric proton channel activated by low pH. The His37-Trp41 quartet is the heart of acid activation and proton conductance, but the functional mechanism is still controversial. We carried out ab initio calculations to model the pH-dependent structures of the His37-Trp41 quartet. In our model at neutral pH, the four His37 residues are configured into a pair of dimers; in each dimer, a proton is shared between Nδ1 on one residue and Nε2 on the other, and, under the restraint of the backbone, the two imidazole rings are nearly parallel, in contrast to a perpendicular arrangement for a free imidazole-imidazolium dimer. Within each dimer the +1 charge is highly delocalized, contributing to its stabilization in a low dielectric environmen

SUBMITTER: Dong H 

PROVIDER: S-EPMC3733280 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature