Toll-like receptor 5 from Ctenopharyngodon idella

Abstract

TLR5 is a pattern recognition receptor involved in the innate immune response. It is highly expressed on the cell membranes of intestine epithelial cells and dendritic cells, and it is the only human TLR known to bind a protein ligand. The ligand for TLR5 is bacterial flagellin, which binds to TLR5, inducing dimerization and triggering the innate immune response. Consequently, defects in TLR5 can impact inflammatory diseases of the gut, autoimmune diseases, and cancer cell growth. While the structure of zebrafish TLR5-LRR14 VLR in complex with flagellin has been determined through X-ray crystallography, understanding the precise mechanisms of flagellin recognition and signal transduction by TLR5 requires the full-length structure. In this study, I expressed Ctenopharyngodon idella (Grass carp) Toll-like receptor 5a and 5b, and using Cryo-EM, I determined the structures of TLR5a in its apo state, both as a dimer and a tetramer.