6VIE
Structure of caspase-1 in complex with gasdermin D
Summary for 6VIE
| Entry DOI | 10.2210/pdb6vie/pdb |
| Descriptor | Caspase-1 subunit p20, Caspase-1 subunit p10, Gasdermin-D (3 entities in total) |
| Functional Keywords | dual site recognition, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 133602.20 |
| Authors | Liu, Z.,Xiao, T.S. (deposition date: 2020-01-13, release date: 2020-07-01, Last modification date: 2023-10-11) |
| Primary citation | Liu, Z.,Wang, C.,Yang, J.,Chen, Y.,Zhou, B.,Abbott, D.W.,Xiao, T.S. Caspase-1 Engages Full-Length Gasdermin D through Two Distinct Interfaces That Mediate Caspase Recruitment and Substrate Cleavage. Immunity, 53:106-, 2020 Cited by PubMed Abstract: The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation. Previous work has identified cleavage site signatures in substrates such as GSDMD, but it is unclear whether these are the sole determinants for caspase engagement. Here we report the crystal structure of a complex between human caspase-1 and the full-length murine GSDMD. In addition to engagement of the GSDMD N- and C-domain linker by the caspase-1 active site, an anti-parallel β sheet at the caspase-1 L2 and L2' loops bound a hydrophobic pocket within the GSDMD C-terminal domain distal to its N-terminal domain. This "exosite" interface endows an additional function for the GSDMD C-terminal domain as a caspase-recruitment module besides its role in autoinhibition. Our study thus reveals dual-interface engagement of GSDMD by caspase-1, which may be applicable to other physiological substrates of caspases. PubMed: 32553275DOI: 10.1016/j.immuni.2020.06.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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