{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["637(8045)"],"submitter":["Pourmal S"],"pubmed_abstract":["Lytic cell death culminates in plasma membrane rupture, which releases large intracellular molecules to augment the inflammatory response. Plasma membrane rupture is mediated by the effector membrane protein ninjurin-1 (NINJ1)<sup>1</sup>, which polymerizes and ruptures the membrane via its hydrophilic face<sup>1-4</sup>. How NINJ1 is restrained under steady-state conditions to ensure cell survival remains unknown. Here we describe the molecular underpinnings of NINJ1 inhibition. Using cryogenic electron microscopy, we determined the structure of inactive-state mouse NINJ1 bound to the newly developed nanobody Nb538. Inactive NINJ1 forms a face-to-face homodimer by adopting a three-helix conformation with unkinked transmembrane helix 1 (TM1), in contrast to the four-helix TM1-kinked active"],"journal":["Nature"],"pagination":["446-452"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11711097"],"repository":["biostudies-literature"],"pubmed_title":["Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture."],"pmcid":["PMC11711097"],"pubmed_authors":["Zhou L","Gupta S","Stowe IB","Rohou A","Newton K","Alegre K","Kayagaki N","Yang Y","Johnson MC","Zhang Y","Chen PA","Dixit VM","Pourmal S","Truong ME","Deshpande I"],"additional_accession":[]},"is_claimable":false,"name":"Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture.","description":"Lytic cell death culminates in plasma membrane rupture, which releases large intracellular molecules to augment the inflammatory response. Plasma membrane rupture is mediated by the effector membrane protein ninjurin-1 (NINJ1)<sup>1</sup>, which polymerizes and ruptures the membrane via its hydrophilic face<sup>1-4</sup>. How NINJ1 is restrained under steady-state conditions to ensure cell survival remains unknown. Here we describe the molecular underpinnings of NINJ1 inhibition. Using cryogenic electron microscopy, we determined the structure of inactive-state mouse NINJ1 bound to the newly developed nanobody Nb538. Inactive NINJ1 forms a face-to-face homodimer by adopting a three-helix conformation with unkinked transmembrane helix 1 (TM1), in contrast to the four-helix TM1-kinked active","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-02T08:05:03.225Z","creation":"2026-04-16T03:10:42.185Z"},"accession":"S-EPMC11711097","cross_references":{"pubmed":["39476863"],"doi":["10.1038/s41586-024-08273-4"]}}