9wff | pdb_00009wff

Cryo-EM structure of the human Erlin2 oligomer

spinqualitylabelsall models 9wff, resolution 2.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wff is a 26 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.12Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ERLN2_HUMAN Juvenile primary lateral sclerosis;Recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome;Autosomal spastic paraplegia type 18. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Function ERLN2_HUMAN Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:17502376, PubMed:19240031). Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618). Publication Abstract from PubMed The 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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