6AO3

Crystal structure of the murine gasdermin D C-terminal domain

6AO3 の概要

• エントリーDOI: 10.2210/pdb6ao3/pdb
• 分子名称: Gasdermin-D (2 entities in total)
• 機能のキーワード: inflammasome, pyroptosis, gasdermin d, autoinhibition, salmonella infection, immune system
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 92052.70

構造登録者

Liu, Z.,Wang, C.,Yang, J.,Xiao, T.S. (登録日: 2017-08-15, 公開日: 2018-04-11, 最終更新日: 2024-03-13)

主引用文献

Liu, Z.,Wang, C.,Rathkey, J.K.,Yang, J.,Dubyak, G.R.,Abbott, D.W.,Xiao, T.S.
Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition.
Structure, 26:778-784.e3, 2018

PubMed Abstract: Pyroptosis is an inflammatory form of programmed cell death that plays important roles in immune protection against infections and in inflammatory disorders. Gasdermin D (GSDMD) is an executor of pyroptosis upon cleavage by caspases-1/4/5/11 following canonical and noncanonical inflammasome activation. GSDMD N-terminal domain assembles membrane pores to induce cytolysis, whereas its C-terminal domain inhibits cell death through intramolecular association with the N domain. The molecular mechanisms of autoinhibition for GSDMD are poorly characterized. Here we report the crystal structures of the human and murine GSDMD C-terminal domains, which differ from those of the full-length murine GSDMA3 and the human GSDMB C-terminal domain. Mutations of GSDMD C-domain residues predicted to locate at its interface with the N-domain enhanced pyroptosis. Our results suggest that GSDMDs may employ a distinct mode of intramolecular domain interaction and autoinhibition, which may be relevant to its unique role in pyroptosis downstream of inflammasome activation.

PubMed: 29576317
DOI: 10.1016/j.str.2018.03.002

実験手法

X-RAY DIFFRACTION (1.76 Å)