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

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.

Abbreviations
A2A	=	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

Communicated by Ramaswamy H. Sarma

Keywords:

• Flagellin
• conformational thermodynamics
• molecular dynamics simulation
• immune response

Acknowledgements

SD thanks DST INSPIRE for fellowship. JC and MG thank DST, Government of India for funding. We thank S. S. Das for helpful discussions.

Disclosure statement

No potential conflict of interest was reported by the authors.