生物
膜
生物物理学
低聚物
细胞膜
跨膜蛋白
材料科学
化学
生物化学
高分子化学
受体
作者
Liron David,Jazlyn P. Borges,Louis Hollingsworth,Allen Volchuk,Isabelle Jansen,Evelyn Garlick,Benjamin E. Steinberg,Hao Wu
出处
期刊:Cell
[Elsevier]
日期:2024-04-01
卷期号:187 (9): 2224-2235.e16
被引量:9
标识
DOI:10.1016/j.cell.2024.03.008
摘要
Summary
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.
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