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-Structure paper
タイトル | Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins. |
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ジャーナル・号・ページ | Mol Cell, Vol. 84, Issue 17, Page 3302-3319.e11, Year 2024 |
掲載日 | 2024年9月5日 |
![]() | 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 / ![]() |
PubMed 要旨 | 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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手法 | EM (単粒子) |
解像度 | 3.65 - 8.85 Å |
構造データ | ![]() EMDB-45293: Structure of the human BOS complex in GDN EMDB-45294, PDB-9c7u: EMDB-45295, PDB-9c7v: |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | MEMBRANE PROTEIN / membrane protein biogenesis / membrane protein complex |