8S9S

Structure of the human ER membrane protein complex (EMC) in GDN

これはPDB形式変換不可エントリーです。

8S9S の概要

• エントリーDOI: 10.2210/pdb8s9s/pdb
• EMDBエントリー: 40245
• 分子名称: ER membrane protein complex subunit 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• 機能のキーワード: insertase, endoplasmic reticulum, transmembrane chaperone, 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: 307492.80

構造登録者

Tomaleri, G.P.,Nguyen, V.N.,Voorhees, R.M. (登録日: 2023-03-30, 公開日: 2023-05-17, 最終更新日: 2024-11-13)

主引用文献

Pleiner, T.,Hazu, M.,Pinton Tomaleri, G.,Nguyen, V.N.,Januszyk, K.,Voorhees, R.M.
A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.
J.Cell Biol., 222:-, 2023

PubMed Abstract: Tail-anchored (TA) proteins play essential roles in mammalian cells, and their accurate localization is critical for proteostasis. Biophysical similarities lead to mistargeting of mitochondrial TA proteins to the ER, where they are delivered to the insertase, the ER membrane protein complex (EMC). Leveraging an improved structural model of the human EMC, we used mutagenesis and site-specific crosslinking to map the path of a TA protein from its cytosolic capture by methionine-rich loops to its membrane insertion through a hydrophilic vestibule. Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TA proteins. Similarly, this selectivity filter retains the positively charged soluble domains of multipass substrates in the cytosol, thereby ensuring they adopt the correct topology and enforcing the "positive-inside" rule. Substrate discrimination by the EMC provides a biochemical explanation for one role of charge in TA protein sorting and protects compartment integrity by limiting protein misinsertion.

PubMed: 37199759
DOI: 10.1083/jcb.202212007

実験手法

ELECTRON MICROSCOPY (3.6 Å)