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TitleCryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization.
Journal, issue, pagesScience, Vol. 350, Issue 6259, Page 404-409, Year 2015
Publish dateOct 23, 2015
AuthorsLiman Zhang / Shuobing Chen / Jianbin Ruan / Jiayi Wu / Alexander B Tong / Qian Yin / Yang Li / Liron David / Alvin Lu / Wei Li Wang / Carolyn Marks / Qi Ouyang / Xinzheng Zhang / Youdong Mao / Hao Wu /
PubMed AbstractThe NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the ...The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90° hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.
External linksScience / PubMed:26449474 / PubMed Central
MethodsEM (single particle)
Resolution4.7 - 12.5 Å
Structure data

6458

3jbl

EMDB-6458, PDB-3jbl:
Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-6459:
Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization
Method: EM (single particle) / Resolution: 7.5 Å

EMDB-6460:
Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization
Method: EM (single particle) / Resolution: 12.5 Å

Source
  • mus musculus (house mouse)
KeywordsIMMUNE SYSTEM / Inflammasome / NLRC4 / NAIP2

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