6KXG

Crystal structure of caspase-11-CARD

Summary for 6KXG

• Entry DOI: 10.2210/pdb6kxg/pdb
• Descriptor: caspase-11-CARD (2 entities in total)
• Functional Keywords: card, inflammasome, caspase-11, immune system
• Biological source: Mus musculus
• Total number of polymer chains: 4
• Total formula weight: 203742.67

Authors

Liu, M.Z.Y.,Jin, T.C. (deposition date: 2019-09-11, release date: 2020-09-16, Last modification date: 2023-11-22)

Primary citation

Liu, M.,Zhou, K.,Xu, Z.,Ma, H.,Cao, X.,Yin, X.,Zeng, W.,Zahid, A.,Fu, S.,Ni, K.,Ye, X.,Zhou, Y.,Bai, L.,Zhou, R.,Jin, T.
Crystal structure of caspase-11 CARD provides insights into caspase-11 activation.
Cell Discov, 6:70-70, 2020

PubMed Abstract: Murine caspase-11 is the centerpiece of the non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) and a C-terminal catalytic domain. The aggregation of caspase-11 is thought to promote the auto-processing and activation of caspase-11. However, the activation mechanism of caspase-11 remains unclear. In this study, we purified the caspase-11 CARD fused to an MBP tag and found it tetramerizes in solution. Crystallographic analysis reveals an extensive hydrophobic interface formed by the H1-2 helix mediating homotypic CARD interactions. Importantly, mutations of the helix H1-2 hydrophobic residues abolished the tetramerization of MBP-tagged CARD in solution and failed to induce pyroptosis in cells. Our study provides the first evidence of the homotypic interaction mode for an inflammatory caspase by crystal model. This finding demonstrates that the tetramerization of the N-terminal CARD can promote releasing of the catalytic domain auto-inhibition, leading to the caspase-11 activation.

PubMed: 33083005
DOI: 10.1038/s41421-020-00201-w

Experimental method

X-RAY DIFFRACTION (2.805 Å)