8JYV

Crystal structure of the gasdermin from Trichoplax adhaerens

8JYV の概要

• エントリーDOI: 10.2210/pdb8jyv/pdb
• 分子名称: Gasdermin pore forming domain-containing protein (2 entities in total)
• 機能のキーワード: pyroptosis, gasdermnin, immune system
• 由来する生物種: Trichoplax adhaerens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26246.66

構造登録者

Zeng, H.,Hou, Y.J.,Ding, J. (登録日: 2023-07-04, 公開日: 2024-05-01, 最終更新日: 2024-05-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.86 Å)