6VIE

Structure of caspase-1 in complex with gasdermin D

6VIE の概要

• エントリーDOI: 10.2210/pdb6vie/pdb
• 分子名称: Caspase-1 subunit p20, Caspase-1 subunit p10, Gasdermin-D (3 entities in total)
• 機能のキーワード: dual site recognition, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 133602.20

構造登録者

Liu, Z.,Xiao, T.S. (登録日: 2020-01-13, 公開日: 2020-07-01, 最終更新日: 2023-10-11)

主引用文献

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

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: 32553275
DOI: 10.1016/j.immuni.2020.06.007

実験手法

X-RAY DIFFRACTION (3.4 Å)