7ADP

Cryo-EM structure of human ER membrane protein complex in GDN detergent

7ADP の概要

• エントリーDOI: 10.2210/pdb7adp/pdb
• 関連するPDBエントリー: 7ADO
• EMDBエントリー: 11732 11733
• 分子名称: ER membrane protein complex subunit 1, ER membrane protein complex subunit 2, ER membrane protein complex subunit 3, ... (9 entities in total)
• 機能のキーワード: er membrane protein, emc, membrane protein biogenesis, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 276505.75

構造登録者

Braeuning, B.,Prabu, J.R.,Miller-Vedam, L.E.,Weissman, J.S.,Frost, A.,Schulman, B.A. (登録日: 2020-09-15, 公開日: 2020-12-02, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.6 Å)