6AO4

Crystal structure of the human gasdermin D C-terminal domain

Summary for 6AO4

• Entry DOI: 10.2210/pdb6ao4/pdb
• Descriptor: Gasdermin-D (1 entity in total)
• Functional Keywords: inflammasome, pyroptosis, gasdermin d, autoinhibition, salmonella infection, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 22354.44

Authors

Liu, Z.,Wang, C.,Yang, J.,Xiao, T.S. (deposition date: 2017-08-15, release date: 2018-04-11, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.901 Å)