9VVJ

Cryo-EM structure of the erlin1/2 complex purified using DDM and GDN

Summary for 9VVJ

• Entry DOI: 10.2210/pdb9vvj/pdb
• EMDB information: 65382
• Descriptor: Erlin-1, Erlin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cryo-em, complex, membrane protein, spfh protein family
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 26
• Total formula weight: 903488.49

Authors

Yan, L.,Gao, N. (deposition date: 2025-07-15, release date: 2026-03-25, Last modification date: 2026-04-22)

Primary citation

Yan, L.,Xu, Z.,Yao, Y.,Awang, T.,Wang, X.,Wang, Y.,Ma, C.,Li, N.,Song, C.,Chen, X.W.,Gao, N.
The Erlin1/2 complex is a dynamic scaffold for membrane microdomain assembly on the endoplasmic reticulum.
Mol.Cell, 86:1362-1376.e5, 2026

PubMed Abstract: The SPFH (stomatin, prohibitin, flotillin, and HflK/C) family proteins are proposed scaffolds for organizing functional membrane microdomains (FMMs) on various cellular membranes. Erlin1 and Erlin2, two endoplasmic reticulum (ER)-residing SPFH members, as heteromeric complexes, participate in ER-associated protein degradation (ERAD). However, the mechanisms underlying Erlin-mediated FMM organization and ERAD regulation remain poorly understood. Here, through cryoelectron microscopy (cryo-EM), we find that the human Erlin1/2 complex forms a 26-mer cage assembly, defining a nanometer-sized microdomain on the luminal leaflet. The intramembrane region of each subunit constitutes a specific phosphatidylinositol-binding pocket. ER proteins can be recruited to both the interior and exterior of these cages. By caging cargoes, the Erlin1/2 complex physically secludes them from their substrates or binding partners, conferring another layer of regulation on their functions. Moreover, individual cages can cluster to organize FMMs of different sizes. These dynamic properties underscore a general regulatory role of Erlin1/2 in various ER-related biological processes, including coronaviral replication.

PubMed: 41887216
DOI: 10.1016/j.molcel.2026.03.001

Experimental method

ELECTRON MICROSCOPY (2.6 Å)