期刊
SCIENCE
卷 350, 期 6259, 页码 404-409出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac5789
关键词
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资金
- NIH K99 grant [AI108793]
- Cancer Research Institute
- Intel academic grant
- Peking University
- NIH [1DP1HD087988]
- NIH grant Center for HIV/AIDS Vaccine Immunology and Immunogen Design (CHAVI-ID) [AI100645]
- NSF [ECS-0335765]
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 similar to 90 degrees 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.
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