Structural insights into the human HRD1 ubiquitin ligase complex.

ABSTRACT: In the endoplasmic reticulum (ER), defective proteins are cleaned via the ER-associated protein degradation (ERAD) pathway. The HRD1 ubiquitin ligase complex, with HRD1, SEL1L, XTP3B or OS9 and Derlin family proteins as the core components, plays essential roles in the recognition, retrotranslocation, and ubiquitination of luminal ERAD substrates. However, the molecular basis is unclear. Here, we determine the cryo-EM structure of the human HRD1-SEL1L-XTP3B complex at 3.3 Å resolution. HRD1 is a dimer, but only one protomer carries the SEL1L-XTP3B complex, forming a 2:1:1 complex. Careful inspection of the EM map reveals a trimmed N-glycan sandwiched by XTP3B and SEL1L, and SEL1L may also contribute to the recognition of the trimmed glycan. The complex undergoes dramatic conformational cha

SUBMITTER: Guo L 

PROVIDER: S-EPMC12217079 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature