| First Author | David L | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 9 | Pages | 2224-2235.e16 |
| PubMed ID | 38614101 | Mgi Jnum | J:348773 |
| Mgi Id | MGI:7626170 | Doi | 10.1016/j.cell.2024.03.008 |
| Citation | David L, et al. (2024) NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. Cell 187(9):2224-2235.e16 |
| abstractText | 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. |
