8J0N

cryo-EM structure of human EMC

8J0N の概要

• エントリーDOI: 10.2210/pdb8j0n/pdb
• EMDBエントリー: 35906
• 分子名称: ER membrane protein complex subunit 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ER membrane protein complex subunit 2, ... (10 entities in total)
• 機能のキーワード: er membrane protein complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 297440.97

構造登録者

Li, M.,Zhang, C.,Wu, J.,Lei, M. (登録日: 2023-04-11, 公開日: 2024-04-03, 最終更新日: 2024-10-23)

主引用文献

Li, M.,Zhang, C.,Xu, Y.,Li, S.,Huang, C.,Wu, J.,Lei, M.
Structural insights into human EMC and its interaction with VDAC.
Aging (Albany NY), 16:5501-5525, 2024

PubMed Abstract: The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking membrane proteins. However, the structural basis and regulation of its multifunctionality remain elusive. Here, we report cryo-electron microscopy structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states at resolutions of 3.47 Å and 3.32 Å, respectively. We discovered a specific interaction between VDAC proteins and the EMC at mitochondria-ER contact sites, which is conserved from yeast to humans. Moreover, we identified a gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion. Conformation changes of this gating plug during the apo-to-VDAC-bound transition reveal that the EMC unlikely acts as an insertase in the VDAC1-bound state. Based on the data analysis, the gating plug may regulate EMC functions by modifying the hydrophilic vestibule in different states. Our discovery offers valuable insights into the structural basis of EMC's multifunctionality.

PubMed: 38517390
DOI: 10.18632/aging.205660

実験手法

ELECTRON MICROSCOPY (3.47 Å)