9C7U

Structure of the human truncated BOS complex in GDN

Summary for 9C7U

• Entry DOI: 10.2210/pdb9c7u/pdb
• EMDB information: 45293 45294 45295
• Descriptor: Nicalin, BOS complex subunit NOMO2, Transmembrane protein 147, ... (4 entities in total)
• Functional Keywords: membrane protein biogenesis, membrane protein complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 130937.16

Authors

Nguyen, V.N.,Tomaleri, G.P.,Voorhees, R.M. (deposition date: 2024-06-11, release date: 2024-08-21, Last modification date: 2024-10-16)

Primary citation

Page, K.R.,Nguyen, V.N.,Pleiner, T.,Tomaleri, G.P.,Wang, M.L.,Guna, A.,Hazu, M.,Wang, T.Y.,Chou, T.F.,Voorhees, R.M.
Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins.
Mol.Cell, 84:3302-, 2024

PubMed Abstract: Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein-coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of Sec61 (BOS) complex, a component of the multipass translocon, was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC⋅BOS holocomplex showed that characteristics of a GPCR's soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, the multipass translocon, and Sec61 for the biogenesis of diverse membrane proteins in human cells.

PubMed: 39173640
DOI: 10.1016/j.molcel.2024.08.005

Experimental method

ELECTRON MICROSCOPY (3.65 Å)