6KI0

Crystal Structure of Human ASC-CARD

Summary for 6KI0

• Entry DOI: 10.2210/pdb6ki0/pdb
• Related PRD ID: PRD_900009
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,Apoptosis-associated speck-like protein containing a CARD, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• Functional Keywords: death domain fold, immune system
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 2
• Total formula weight: 104277.57

Authors

Xu, Z.H.,Jin, T.C. (deposition date: 2019-07-16, release date: 2020-07-22, Last modification date: 2023-11-22)

Primary citation

Xu, Z.,Zhou, Y.,Liu, M.,Ma, H.,Sun, L.,Zahid, A.,Chen, Y.,Zhou, R.,Cao, M.,Wu, D.,Zhao, W.,Li, B.,Jin, T.
Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome.
Cell Death Dis, 12:57-57, 2021

PubMed Abstract: 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 NLRP1 and ASC 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 ASC. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1/ASC 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.

PubMed: 33431827
DOI: 10.1038/s41419-020-03342-8

Experimental method

X-RAY DIFFRACTION (2 Å)