In-silico studies on conformational stability of flagellin–receptor complexes
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 receptor
DPPCdipalmitoyl phosphatidylcholine
ecdextracellular domain
ecl2extracellular loop 2
eLRRextracellular Leucine rich repeat domain
flaDflagellin of Vibrio cholerae
fliCflagellin of Salmonella typhimurium
HPVhyper-variable
MDmolecular dynamics
RMSDroot means squared deviation
TIRtoll-interleukin receptor
TLR5toll like receptor 5
VPAC1vasoactive intestinal peptide receptor
adenosine receptor
dipalmitoyl phosphatidylcholine
extracellular domain
extracellular loop 2
extracellular Leucine rich repeat domain
flagellin of Vibrio cholerae
flagellin of Salmonella typhimurium
hyper-variable
molecular dynamics
root means squared deviation
toll-interleukin receptor
toll like receptor 5
vasoactive intestinal peptide receptor
Communicated by Ramaswamy H. Sarma