The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion

Abstract

Another spin at the wheel The NLR (nucleotide-binding domain leucine-rich repeat) proteins are a key intracellular component of the early innate immune response to pathogens. After binding microbial ligands, assorted NLR family members assemble to form enormous signaling complexes (inflammasomes), which promote pro-inflammatory cytokine secretion and cell death. Tenthorey et al. used cryo-electron microscopy to visualize an assembled ligand-bound inflammasome. They find that when NAIP5 binds flagellin, it changes conformation, which triggers a rotation in monomeric NLRC4, catalyzing further NLRC4 recruitment. Steric clash results in a partially open structure, in contrast with previous descriptions of a closed symmetrical “wheel.” Furthermore, NAIP5 recognizes multiple regions of its ligand, and mutations of flagellin that allow for NAIP5 evasion compromise bacterial fitness. Science , this issue p. 888