- EMDB-45295: Structure of the human BOS:human EMC complex in GDN -
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Entry
Database: EMDB / ID: EMD-45295
Title
Structure of the human BOS:human EMC complex in GDN
Map data
Sharpened map of human BOS:human EMC complex
Sample
Complex: Human BOS complex
Protein or peptide: x 12 types
Ligand: x 1 types
Keywords
membrane protein biogenesis / membrane protein complex / MEMBRANE PROTEIN
Function / homology
Function and homology information
negative regulation of nodal signaling pathway / multi-pass transmembrane protein insertion into ER membrane / multi-pass translocon complex / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / determination of left/right asymmetry in lateral mesoderm ...negative regulation of nodal signaling pathway / multi-pass transmembrane protein insertion into ER membrane / multi-pass translocon complex / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / determination of left/right asymmetry in lateral mesoderm / tail-anchored membrane protein insertion into ER membrane / protein localization to nuclear inner membrane / Miscellaneous transport and binding events / cobalt ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / copper ion transport / regulation of protein complex stability / magnesium ion transmembrane transporter activity / autophagosome assembly / RHOA GTPase cycle / regulation of signal transduction / regulation of protein-containing complex assembly / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / positive regulation of angiogenesis / ribosome binding / carbohydrate binding / early endosome membrane / angiogenesis / nuclear membrane / early endosome / protein stabilization / Golgi membrane / apoptotic process / endoplasmic reticulum membrane / endoplasmic reticulum / Golgi apparatus / protein-containing complex / extracellular region / membrane / plasma membrane / cytoplasm Similarity search - Function
: / : / : / : / : / : / : / : / : / : ...: / : / : / : / : / : / : / : / : / : / BOS complex subunit NOMO1-like, first beta sandwich domain / BOS complex subunit NOMO1-like, beta sandwich domain / BOS complex subunit NOMO1-like, second beta sandwich domain / NOMO Ig-like domain / NOMO C-terminal transthyretin-like domain / NOMO third transthyretin-like domain / NOMO fifth transthyretin-like domain / NOMO sixth transthyretin-like domain / NOMO eighth prealbumin-like domain / Nicalin / Transmembrane protein 147 / Predicted membrane protein (DUF2053) / ER membrane protein complex subunit 8/9 / : / Uncharacterised protein family (UPF0172) / Carboxypeptidase regulatory-like domain / 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, C-terminal / 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 / Carboxypeptidase-like, regulatory domain superfamily / Prealbumin-like fold domain / Prealbumin-like fold domain / Carbohydrate-binding-like fold / Pyrrolo-quinoline quinone repeat / Outer membrane protein assembly factor BamB / Peptidase M28 / Peptidase family M28 / 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 / Immunoglobulin-like fold Similarity search - Domain/homology
ER membrane protein complex subunit 8 / ER membrane protein complex subunit 2 / ER membrane protein complex subunit 4 / BOS complex subunit NOMO2 / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 5 / ER membrane protein complex subunit 1 / BOS complex subunit NCLN / ER membrane protein complex subunit 6 / BOS complex subunit TMEM147 ...ER membrane protein complex subunit 8 / ER membrane protein complex subunit 2 / ER membrane protein complex subunit 4 / BOS complex subunit NOMO2 / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 5 / ER membrane protein complex subunit 1 / BOS complex subunit NCLN / ER membrane protein complex subunit 6 / BOS complex subunit TMEM147 / Endoplasmic reticulum membrane protein complex subunit 7 / ER membrane protein complex subunit 3 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 6.6 Å
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
DP2 GM137412
United States
Heritage Medical Research Institute
United States
Citation
Journal: Mol Cell / Year: 2024 Title: Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins. Authors: Katharine R Page / Vy N Nguyen / Tino Pleiner / Giovani Pinton Tomaleri / Maxine L Wang / Alina Guna / Masami Hazu / Ting-Yu Wang / Tsui-Fen Chou / Rebecca M Voorhees / Abstract: Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we ...Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein-coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of Sec61 (BOS) complex, a component of the multipass translocon, was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC⋅BOS holocomplex showed that characteristics of a GPCR's soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, the multipass translocon, and Sec61 for the biogenesis of diverse membrane proteins in human cells.
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