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-Structure paper
タイトル | NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. |
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ジャーナル・号・ページ | Cell, Vol. 187, Issue 9, Page 2224-2235.e16, Year 2024 |
掲載日 | 2024年4月25日 |
著者 | Liron David / Jazlyn P Borges / L Robert Hollingsworth / Allen Volchuk / Isabelle Jansen / Evelyn Garlick / Benjamin E Steinberg / Hao Wu / |
PubMed 要旨 | 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. ...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. |
リンク | Cell / PubMed:38614101 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.3 Å |
構造データ | EMDB-42301, PDB-8uip: |
由来 |
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キーワード | IMMUNE SYSTEM / Ninjurin1 / NINJ1 / inflammation / inflammasome / pyroptosis / plasma membrane rupture |