ArticleNature communications2026
Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Functional integrity of the SEL1L-HRD1 complex is critical for endoplasmic reticulum-associated degradation and organismal viability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lipid bilayer thinning near a ubiquitin ligase selects ER membrane proteins for degradation.bioRxiv : the preprint server for biology · 2025Article
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5 authors.
Funding
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 (Gly585Asp) and SEL1L-HRD1 (Ser658Pro) interfaces disrupt complex formation and impair ERAD activity. A newly identified disease-associated HRD1 variant (Ala91Asp), located in transmembrane helix 3, impairs HRD1 dimerization and substrate processing. These findings provide structural and functional insights for mammalian SEL1L-HRD1 ERAD and elucidate how mutations destabilizing this machinery contribute to human disease.
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