{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin LL"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["2064"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12949252"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["The SEL1L-HRD1 complex represents the most conserved branch of endoplasmic reticulum (ER)-associated degradation (ERAD), a critical quality-control pathway that clears misfolded ER proteins. However, the molecular organization and pathogenic mechanisms of mammalian ERAD have remained elusive. Here, we report the cryo-EM structure of the core mammalian ERAD complex, comprising the ER lectin OS9, SEL1L, and the E3 ubiquitin ligase HRD1. The structure, validated by mutagenesis and crosslinking assays, reveals a dimeric assembly of the core complex in which SEL1L and OS9 form a claw-like configuration in the ER lumen that mediates substrate engagement, while HRD1 dimerizes within the membrane that may facilitate substrate translocation. Furthermore, pathogenic SEL1L mutations at the SEL1L-OS9 "],"journal":["Nature communications"],"pubmed_title":["Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex."],"pmcid":["PMC12949252"],"funding_grant_id":["R35GM130292","R01DK120047","R01DK120330"],"pubmed_authors":["Qi L","Lin LL","Maldosevic E","Jomaa A","Zhou LE"],"additional_accession":[]},"is_claimable":false,"name":"Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.","description":"The SEL1L-HRD1 complex represents the most conserved branch of endoplasmic reticulum (ER)-associated degradation (ERAD), a critical quality-control pathway that clears misfolded ER proteins. However, the molecular organization and pathogenic mechanisms of mammalian ERAD have remained elusive. Here, we report the cryo-EM structure of the core mammalian ERAD complex, comprising the ER lectin OS9, SEL1L, and the E3 ubiquitin ligase HRD1. The structure, validated by mutagenesis and crosslinking assays, reveals a dimeric assembly of the core complex in which SEL1L and OS9 form a claw-like configuration in the ER lumen that mediates substrate engagement, while HRD1 dimerizes within the membrane that may facilitate substrate translocation. Furthermore, pathogenic SEL1L mutations at the SEL1L-OS9 ","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-16T23:28:30.311Z","creation":"2026-07-12T03:11:14.607Z"},"accession":"S-EPMC12949252","cross_references":{"pubmed":["41593065"],"doi":["10.1038/s41467-026-68777-7"]}}