Zhihao's manuscript was published
Release time:2021-05-18 Browse:104


 Zhihao's manuscript titled with Homotypic CARD-CARD interaction is critical for
the activation of NLRP1 inflammasome was published online at
 Cell Death & Disease on Jan 11, 2021. Congratulations. 

Currently, the first author of this paper, Zhihao Xu, is a 2rd year Ph.D student at USTC. Prof. Tengchuan Jin and Prof. Bofeng Li of First affiliated hospital of USTC are corresponding authors. Congratulations to all authors. 


Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD–CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASCCARD. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1CARD/ASCCARD complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.