7KTX

Cryo-EM structure of Saccharomyces cerevisiae ER membrane protein complex bound to a Fab in DDM detergent

Summary for 7KTX

• Entry DOI: 10.2210/pdb7ktx/pdb
• EMDB information: 11732 11733 23003 23033
• Descriptor: ER membrane protein complex subunit 1, Fab DH4 light chain, Unassigned helix, ... (12 entities in total)
• Functional Keywords: er membrane protein complex, emc, membrane protein biogenesis, insertase, chaperone, endoplasmic, reticulum, membrane protein-immune system complex, membrane protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 311204.36

Authors

Miller-Vedam, L.E.,Schirle Oakdale, N.S.,Braeuning, B.,Boydston, E.A.,Sevillano, N.,Popova, K.D.,Bonnar, J.L.,Shurtleff, M.J.,Prabu, J.R.,Stroud, R.M.,Craik, C.S.,Schulman, B.A.,Weissman, J.S.,Frost, A. (deposition date: 2020-11-24, release date: 2020-12-02, Last modification date: 2024-10-30)

Primary citation

Miller-Vedam, L.E.,Brauning, B.,Popova, K.D.,Schirle Oakdale, N.T.,Bonnar, J.L.,Prabu, J.R.,Boydston, E.A.,Sevillano, N.,Shurtleff, M.J.,Stroud, R.M.,Craik, C.S.,Schulman, B.A.,Frost, A.,Weissman, J.S.
Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients.
Elife, 9:-, 2020

PubMed Abstract: Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC's multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes.

PubMed: 33236988
DOI: 10.7554/eLife.62611

Experimental method

ELECTRON MICROSCOPY (4.3 Å)