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

DPPC

dipalmitoyl phosphatidylcholine

ecd

extracellular domain

ecl2

extracellular loop 2

eLRR

extracellular Leucine rich repeat domain

flaD

flagellin of Vibrio cholerae

fliC

flagellin of Salmonella typhimurium

HPV

hyper-variable

MD

molecular dynamics

RMSD

root means squared deviation

TIR

toll-interleukin receptor

TLR5

toll like receptor 5

VPAC1

vasoactive 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