Structural determinants of V. cholerae CheYs that discriminate them in FliM binding:: Comparative modeling and MD simulation studies

Chemotaxis of Vibrio cholerae is a complex process where multiple paralogues of various chemotaxis genes participate. V. cholerae contains five copies of the response regulator protein CheY (CheY(v)) and the role played by these CheY homologs in chemotaxis and virulence are investigated only through a few in vivo studies. As identification of the molecular features that discriminate CheY(v)s in terms of FliM binding is necessary for the detailed understanding of chemotaxis and pathogenesis, we built the models of CheY(v)s through comparative modeling and MD simulation was performed on each model in their phosphorylated and Mg+2 bound state. Our analysis identified the key structural elements, unique to CheY3(v), which complement the N-terminal part of FliM(v) and we explained how the structure, shape, and surface properties of the FliM binding pocket of other CheY(v)s abrogate this function. Furthermore, we have provided the structural basis of a putative cross species interaction between CheY(E) and FliM(v), identified in a recent in vivo study.