Structural and biochemical basis for induced self-propagation of NLRC4

Zehan Hu, Qiang Zhou, Chenlu Zhang, Shilong Fan, Wei Cheng, Yue Zhao, Feng Shao, Hong Wei Wang, Sen Fang Sui, Jijie Chai

Research output: Contribution to journalArticlepeer-review

245 Scopus citations


Responding to stimuli, nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs) oligomerize into multiprotein complexes, termed inflammasomes, mediating innate immunity. Recognition of bacterial pathogens by NLR apoptosis inhibitory proteins (NAIPs) induces NLR family CARD domain-containing protein 4 (NLRC4) activation and formation of NAIP-NLRC4 inflammasomes. The wheel-like structure of a PrgJ-NAIP2-NLRC4 complex determined by cryogenic electron microscopy at 6.6 angstrom reveals that NLRC4 activation involves substantial structural reorganization that creates one oligomerization surface (catalytic surface). Once activated, NLRC4 uses this surface to catalyze the activation of an inactive NLRC4, self-propagating its active conformation to form the wheel-like architecture. NAIP proteins possess a catalytic surface matching the other oligomerization surface (receptor surface) of NLRC4 but not those of their own, ensuring that one NAIP is sufficient to initiate NLRC4 oligomerization.

Original languageEnglish (US)
Pages (from-to)399-404
Number of pages6
Issue number6259
StatePublished - Oct 23 2015
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Structural and biochemical basis for induced self-propagation of NLRC4'. Together they form a unique fingerprint.

Cite this