- EMDB-74981: The ER membrane protein complex acts as a chaperone to promote vo... -
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基本情報
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データベース: EMDB / ID: EMD-74981
タイトル
The ER membrane protein complex acts as a chaperone to promote voltage-gated calcium channel assembly
マップデータ
Non-uniform refied z flipped map
試料
複合体: Structure of the human ER membrane protein complex (EMC) with Nanobodies E2 and G9
タンパク質・ペプチド: x 11種
リガンド: x 1種
キーワード
protein biogenesis / endoplasmic reticulum / ER / chaperone / insertase / complex / membrane protein / CHAPERONE-IMMUNE SYSTEM complex
機能・相同性
機能・相同性情報
extrinsic component of endoplasmic reticulum membrane / EMC complex / : / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / tail-anchored membrane protein insertion into ER membrane / Miscellaneous transport and binding events / cobalt ion transmembrane transporter activity / ferrous iron transmembrane transporter activity ...extrinsic component of endoplasmic reticulum membrane / EMC complex / : / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / tail-anchored membrane protein insertion into ER membrane / Miscellaneous transport and binding events / cobalt ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / copper ion transport / magnesium ion transmembrane transporter activity / RHOA GTPase cycle / autophagosome assembly / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / positive regulation of angiogenesis / carbohydrate binding / early endosome membrane / angiogenesis / early endosome / Golgi membrane / apoptotic process / endoplasmic reticulum membrane / endoplasmic reticulum / Golgi apparatus / protein-containing complex / extracellular region / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能
EMC1 N-terminal beta-propeller domain / ER membrane protein complex subunit 8/9 / : / Uncharacterised protein family (UPF0172) / EMC2 TPR-like repeat domain / TMEM85/ER membrane protein complex subunit 4 / ER membrane protein complex subunit 4 / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 7 / ER membrane protein complex subunit 7, beta-sandwich domain ...EMC1 N-terminal beta-propeller domain / ER membrane protein complex subunit 8/9 / : / Uncharacterised protein family (UPF0172) / EMC2 TPR-like repeat domain / TMEM85/ER membrane protein complex subunit 4 / ER membrane protein complex subunit 4 / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 7 / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 6 / ER membrane protein complex subunit 3 / ER membrane protein complex subunit 1, C-terminal / Membrane magnesium transporter / ER membrane protein complex subunit 1 / ER membrane protein complex subunit 6-like / EMC6 / ER membrane protein complex subunit 1, second beta-propeller / Membrane magnesium transporter / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 2-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein DUF106 / Carbohydrate-binding-like fold / Quinoprotein alcohol dehydrogenase-like superfamily / TPR repeat region circular profile. / TPR repeat profile. / MPN domain / MPN domain profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性
ER membrane protein complex subunit 8 / ER membrane protein complex subunit 2 / ER membrane protein complex subunit 4 / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 5 / ER membrane protein complex subunit 1 / ER membrane protein complex subunit 6 / Endoplasmic reticulum membrane protein complex subunit 7 / ER membrane protein complex subunit 3 類似検索 - 構成要素
ジャーナル: bioRxiv / 年: 2026 タイトル: The ER membrane protein complex acts as a chaperone to promote the biogenesis of multi-bundle membrane proteins. 著者: Marinda Stanton / Bharti Singal / Mahamaya Biswal / Megha Agarwal / Caroline Elizabeth Scheuing / Gerardo Dasaev Vargas / Alex Gao / Casey A Gifford / Tino Pleiner / 要旨: Nearly half of the ~5,000 human membrane proteins need to assemble into stoichiometric complexes as part of their biogenesis at the endoplasmic reticulum (ER) membrane. How ER resident biogenesis ...Nearly half of the ~5,000 human membrane proteins need to assemble into stoichiometric complexes as part of their biogenesis at the endoplasmic reticulum (ER) membrane. How ER resident biogenesis factors coordinate membrane insertion, folding and assembly is not well understood. Here, we demonstrate that the ER membrane protein complex (EMC) insertase additionally acts as a chaperone to facilitate the assembly of heterotrimeric voltage-gated calcium channels (Ca). Using function-separating mutations and inhibitory nanobodies we show that nascent Ca channels are degraded prematurely when EMC's chaperone function is selectively perturbed. Blocking EMC's chaperone function strongly impaired Ca-dependent cardiomyocyte contraction. EMC engagement of the pore-forming Caα-subunit occurred co-translationally and required Caα's first transmembrane domain bundle to protrude from the nascent ribosome•Sec61•multipass translocon complex. Our findings establish a chaperone function for the EMC and reveal that biogenesis of multi-bundle membrane proteins requires a highly orchestrated, co-translational interplay between ER biogenesis factors.