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. AbbreviationsA2Aadenosine receptorDPPCdipalmitoyl phosphatidylcholineecdextracellular domainecl2extracellular loop 2eLRRextracellular Leucine rich repeat domainflaDflagellin of Vibrio choleraefliCflagellin of Salmonella typhimuriumHPVhyper-variableMDmolecular dynamicsRMSDroot means squared deviationTIRtoll-interleukin receptorTLR5toll like receptor 5VPAC1vasoactive intestinal peptide receptorCommunicated by Ramaswamy H. Sarma.
Keywords: Flagellin; conformational thermodynamics; immune response; molecular dynamics simulation.