Ribosome-rescuer PELO catalyzes the oligomeric assembly of NLR family proteins via activating their ATPase

Abstract

SUMMARYNOD-like receptors (NLRs) are pattern recognition receptors for diverse innate immune responses. Self-oligomerization after engagement with a ligand was a generally accepted model for the activation of each NLR. We report here that a catalyzer is required for the self-oligomerization. Protein pelota homolog (PELO, Dom34 in yeast), a well-known surveillance factor in translational quality control/ribosome rescue, interacts with all cytosolic NLRs and activates their ATPase. In the case of flagellin-initiated NLRC4 inflammasome activation, flagellin-bound NAIP5 recruits the first NLRC4 and then PELO is required for correctly assembling the rest of NLRC4s into the NLRC4 complex one by one by activating the NLRC4 ATPase. Stoichiometric and functional data revealed that PELO cannot be a structural constituent of NLRC4 inflammasome but a powerful catalyzer for its assembly. The catalytic role of PELO in the activation of cytosolic NLRs is unexpected and may break new ground for future studies of NLR family members.