In-silico studies on conformational stability of flagellin–receptor complexes

Abstract

Abstract Flagellin is a protein, responsible for virulent activities of bacteria. The host cell surface receptor protein TLR5 is known to interact with flagellin in order to activate immune response. However, the underlying microscopic details of this immune response are still elusive. In this study, we report on conformational stability of flagellin of two different organisms known as fliC and flaD in bilayer with reference to water. We find that both the flagellin is conformationally more stable in bilayer than in water. We also observe that fliC–TLR5 and flaD–TLR5 complexes are conformationally stable when the extracellular domain of the protein binds to conserved D1 domain of both fliC and flaD, although the binding interface between fliC–TLR5 and flaD–TLR5 is not identical. Our studies suggest that this might lead to differences in coreceptor bindings involved in immune response and thus have potential application in pharmaceutical developments. AbbreviationsA2A adenosine receptorDPPC dipalmitoyl phosphatidylcholineecd extracellular domainecl2 extracellular loop 2eLRR extracellular Leucine rich repeat domainflaD flagellin of Vibrio choleraefliC flagellin of Salmonella typhimuriumHPV hyper-variableMD molecular dynamicsRMSD root means squared deviationTIR toll-interleukin receptorTLR5 toll like receptor 5VPAC1 vasoactive intestinal peptide receptor Communicated by Ramaswamy H. Sarma