8UIP

Cryo-EM Structure of Human Ninjurin1 curved oligomer

8UIP の概要

• エントリーDOI: 10.2210/pdb8uip/pdb
• EMDBエントリー: 42301
• 分子名称: Ninjurin-1 (1 entity in total)
• 機能のキーワード: ninjurin1, ninj1, inflammation, inflammasome, pyroptosis, plasma membrane rupture, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49070.99

構造登録者

David, L.,Wu, H. (登録日: 2023-10-10, 公開日: 2024-05-01, 最終更新日: 2024-05-08)

主引用文献

David, L.,Borges, J.P.,Hollingsworth, L.R.,Volchuk, A.,Jansen, I.,Garlick, E.,Steinberg, B.E.,Wu, H.
NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks.
Cell, 187:2224-2235.e16, 2024

PubMed Abstract: The membrane protein NINJ1 mediates plasma membrane rupture in pyroptosis and other lytic cell death pathways. Here, we report the cryo-EM structure of a NINJ1 oligomer segmented from NINJ1 rings. Each NINJ1 subunit comprises amphipathic (⍺1, ⍺2) and transmembrane (TM) helices (⍺3, ⍺4) and forms a chain of subunits, mainly by the TM helices and ⍺1. ⍺3 and ⍺4 are kinked, and the Gly residues are important for function. The NINJ1 oligomer possesses a concave hydrophobic side that should face the membrane and a convex hydrophilic side formed by ⍺1 and ⍺2, presumably upon activation. This structural observation suggests that NINJ1 can form membrane disks, consistent with membrane fragmentation by recombinant NINJ1. Live-cell and super-resolution imaging uncover ring-like structures on the plasma membrane that are released into the culture supernatant. Released NINJ1 encircles a membrane inside, as shown by lipid staining. Therefore, NINJ1-mediated membrane disk formation is different from gasdermin-mediated pore formation, resulting in membrane loss and plasma membrane rupture.

PubMed: 38614101
DOI: 10.1016/j.cell.2024.03.008

実験手法

ELECTRON MICROSCOPY (4.3 Å)