9we7 | pdb_00009we7
Cryo-EM structure of RNF170-Erlin1-Erlin2
Structural highlights
DiseaseERLN1_HUMAN Autosomal recessive spastic paraplegia type 62. The disease is caused by variants affecting the gene represented in this entry. FunctionERLN1_HUMAN Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway (PubMed:37683630). Binds cholesterol and may promote ER retention of the SCAP-SREBF complex (PubMed:24217618).[1] [2] [3] (Microbial infection) Required early in hepatitis C virus (HCV) infection to initiate RNA replication, and later in the infection to support infectious virus production.[4] Publication Abstract from PubMedThe endoplasmic reticulum (ER) lipid raft proteins (Erlins) belong to the stomatin-prohibitin-flotillin-HflC/K (SPFH) family and form highly oligomeric platforms that mediate the degradation of activated inositol 1,4,5-trisphosphate receptors by facilitating their interaction with the E3 ligase RNF170. However, the molecular mechanisms underlying this process remain unclear. Here, we successfully reconstituted the Erlin1-Erlin2 complex and its complex with RNF170 by overexpressing these components in HEK293F cells. We also isolated the Erlin2 oligomer by solely expressing Erlin2 in the cells. Using cryo-EM, we determined the structures of the Erlin1-Erlin2 complex, Erlin1-Erlin2-RNF170 complex, and Erlin2 oligomer at resolutions of 3.29 A, 3.05 A, and 2.12 A, respectively. Both the Erlin1-Erlin2 complex and the Erlin2 oligomer exhibit similar cage-like architectures, with the Erlin1-Erlin2 complex containing 13 pairs of Erlin1 and Erlin2 subunits, whereas the Erlin2 oligomer comprises 26 Erlin2. Although RNF170 was clearly identified during protein purification, it was invisible in the final 3D reconstruction, suggesting a high degree of flexibility between RNF170 and the Erlin complex. Multiple water molecules were identified in the Erlin2 oligomer, underscoring their critical roles in facilitating the high degree of oligomerization of the Erlin2 complex. Taken together, our structural investigation elucidates the molecular basis for the assembly of the Erlin complex and provides a framework for further investigation. Structural insights into the organization of the human Erlin complex.,Jia X, Liu G, Li H, Qian H J Mol Cell Biol. 2026 Jan 2:mjaf060. doi: 10.1093/jmcb/mjaf060. PMID:41481136[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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