6CB8

Cryo-EM structure of the Gasdermin A3 membrane pore

6CB8 の概要

• エントリーDOI: 10.2210/pdb6cb8/pdb
• EMDBエントリー: 7449
• 分子名称: Gasdermin-A3, CARDIOLIPIN (2 entities in total)
• 機能のキーワード: pyroptosis, pore forming protein, immune system
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31865.08

構造登録者

Ruan, J.,Wu, H. (登録日: 2018-02-02, 公開日: 2018-04-25, 最終更新日: 2025-06-04)

主引用文献

Ruan, J.,Xia, S.,Liu, X.,Lieberman, J.,Wu, H.
Cryo-EM structure of the gasdermin A3 membrane pore.
Nature, 557:62-67, 2018

PubMed Abstract: Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of pore formation remains unresolved. Here we present the cryo-electron microscopy structures of the 27-fold and 28-fold single-ring pores formed by the N-terminal fragment of mouse GSDMA3 (GSDMA3-NT) at 3.8 and 4.2 Å resolutions, and of a double-ring pore at 4.6 Å resolution. In the 27-fold pore, a 108-stranded anti-parallel β-barrel is formed by two β-hairpins from each subunit capped by a globular domain. We identify a positively charged helix that interacts with the acidic lipid cardiolipin. GSDMA3-NT undergoes radical conformational changes upon membrane insertion to form long, membrane-spanning β-strands. We also observe an unexpected additional symmetric ring of GSDMA3-NT subunits that does not insert into the membrane in the double-ring pore, which may represent a pre-pore state of GSDMA3-NT. These structures provide a basis that explains the activities of several mutant gasdermins, including defective mutants that are associated with cancer.

PubMed: 29695864
DOI: 10.1038/s41586-018-0058-6

実験手法

ELECTRON MICROSCOPY (3.8 Å)