Crystal Structure of NLRC4 Reveals Its Autoinhibition Mechanism

Abstract

Keeping the Inflammasome in Check Nucleotide-binding and oligomerization domain (NOD)–like receptors (NLRs) play an important role in the detection of pathogens by cells of the innate immune system. For several NLR family members, activation results in relief from autoinhibition, oligomerization, and the recruitment of signaling components that together make up the inflammasome, a large multiprotein complex. The inflammasome protects the host by inducing cell death and cytokine secretion. The specific molecular mechanisms that regulate NLR activation and inhibition, however, are not well understood. Hu et al. (p. 172 , published online 13 June) report the crystal structure of autoinhibited NLR family member NLRC4, which reveals the domains that are critical for interaction with adenosine diphosphate to keep NLRC4 in its inactive state and the domains that mediate oligomerization of the protein upon activation.