Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

8GTN

Cryo-EM structure of the gasdermin B pore

This is a non-PDB format compatible entry.
Summary for 8GTN
Entry DOI10.2210/pdb8gtn/pdb
EMDB information34258
DescriptorIsoform 4 of Gasdermin-B (1 entity in total)
Functional Keywordspyroptosis, pore-forming, immune system
Biological sourceHomo sapiens (human)
Total number of polymer chains27
Total formula weight772975.04
Authors
Hou, Y.J.,Cheng, H.,Ding, J. (deposition date: 2022-09-08, release date: 2023-04-12, Last modification date: 2024-07-03)
Primary citationZhong, X.,Zeng, H.,Zhou, Z.,Su, Y.,Cheng, H.,Hou, Y.,She, Y.,Feng, N.,Wang, J.,Shao, F.,Ding, J.
Structural mechanisms for regulation of GSDMB pore-forming activity.
Nature, 616:598-605, 2023
Cited by
PubMed Abstract: Cytotoxic lymphocyte-derived granzyme A (GZMA) cleaves GSDMB, a gasdermin-family pore-forming protein, to trigger target cell pyroptosis. GSDMB and the charter gasdermin family member GSDMD have been inconsistently reported to be degraded by the Shigella flexneri ubiquitin-ligase virulence factor IpaH7.8 (refs. ). Whether and how IpaH7.8 targets both gasdermins is undefined, and the pyroptosis function of GSDMB has even been questioned recently. Here we report the crystal structure of the IpaH7.8-GSDMB complex, which shows how IpaH7.8 recognizes the GSDMB pore-forming domain. We clarify that IpaH7.8 targets human (but not mouse) GSDMD through a similar mechanism. The structure of full-length GSDMB suggests stronger autoinhibition than in other gasdermins. GSDMB has multiple splicing isoforms that are equally targeted by IpaH7.8 but exhibit contrasting pyroptotic activities. Presence of exon 6 in the isoforms dictates the pore-forming, pyroptotic activity in GSDMB. We determine the cryo-electron microscopy structure of the 27-fold-symmetric GSDMB pore and depict conformational changes that drive pore formation. The structure uncovers an essential role for exon-6-derived elements in pore assembly, explaining pyroptosis deficiency in the non-canonical splicing isoform used in recent studies. Different cancer cell lines have markedly different isoform compositions, correlating with the onset and extent of pyroptosis following GZMA stimulation. Our study illustrates fine regulation of GSDMB pore-forming activity by pathogenic bacteria and mRNA splicing and defines the underlying structural mechanisms.
PubMed: 36991125
DOI: 10.1038/s41586-023-05872-5
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.17 Å)
Structure validation

227111

PDB entries from 2024-11-06

PDB statisticsPDBj update infoContact PDBjnumon