Structural basis of TLR5-flagellin recognition and signaling.

The immune system recognizes bacterial infections by binding to conserved molecular fragments derived from the invading bacteria. Molecular mimics of these bacterial determinants have the potential to boost the immunogenicity of vaccines. Yoon et al. (p. [859][1]) now report the crystal structure of the D1/D2 fragment of Salmonella flagellin, a protein critical for the motility of flagellated bacteria, with the ectodomain of zebrafish Toll-like receptor 5 (TLR5), the host receptor that binds to flagellin and signals the immune system to react. Two TLR5-flagellin heterodimers dimerized into a 2:2 tail-to-tail signaling complex. Mutational analysis and use of human TLR5 validated the signaling mechanism, which is conserved from zebrafish to humans. [1]: /lookup/doi/10.1126/science.1215584