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NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks.
David, Liron; Borges, Jazlyn P; Hollingsworth, L Robert; Volchuk, Allen; Jansen, Isabelle; Garlick, Evelyn; Steinberg, Benjamin E; Wu, Hao.
Afiliación
  • David L; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Borges JP; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.
  • Hollingsworth LR; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Volchuk A; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada.
  • Jansen I; Abberior Instruments GmbH, Göttingen, Germany.
  • Garlick E; Abberior Instruments GmbH, Göttingen, Germany.
  • Steinberg BE; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada; Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, ON, Canada; Department of An
  • Wu H; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. Electronic address: wu@crystal.harvard.edu.
Cell ; 187(9): 2224-2235.e16, 2024 Apr 25.
Article en En | MEDLINE | ID: mdl-38614101
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Moléculas de Adhesión Celular Neuronal / Membrana Celular / Microscopía por Crioelectrón Límite: Animals / Humans Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Moléculas de Adhesión Celular Neuronal / Membrana Celular / Microscopía por Crioelectrón Límite: Animals / Humans Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos