8JYZ

Cryo-EM structure of RCD-1 pore from Neurospora crassa

This is a non-PDB format compatible entry.

Summary for 8JYZ

• Entry DOI: 10.2210/pdb8jyz/pdb
• EMDB information: 36734
• Descriptor: Gasdermin-like protein rcd-1-1, Gasdermin-like protein rcd-1-2 (2 entities in total)
• Functional Keywords: pyroptosis, gasdermnin, pore, allorecognition, immune system
• Biological source: Neurospora crassa; More
• Total number of polymer chains: 22
• Total formula weight: 625340.22

Authors

Hou, Y.J.,Sun, Q.,Li, Y.,Ding, J. (deposition date: 2023-07-04, release date: 2024-05-01, Last modification date: 2024-05-29)

Primary citation

Li, Y.,Hou, Y.,Sun, Q.,Zeng, H.,Meng, F.,Tian, X.,He, Q.,Shao, F.,Ding, J.
Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.
Science, 384:adm9190-adm9190, 2024

PubMed Abstract: Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we report two types of cleavage-independent GSDM activation. First, GSDM, a pore-forming domain-only protein from the basal metazoan , is a disulfides-linked autoinhibited dimer activated by reduction of the disulfides. The cryo-electron microscopy (cryo-EM) structure illustrates the assembly mechanism for the 44-mer GSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic () gene in filamentous fungus , are also pore-forming domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in . The cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and a heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs.

PubMed: 38662913
DOI: 10.1126/science.adm9190

Experimental method

ELECTRON MICROSCOPY (3.63 Å)