+
検索条件

キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

-
Structure paper

タイトル	Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3.
ジャーナル・号・ページ	Nature, Vol. 548, Issue 7667, Page 352-355, Year 2017
掲載日	2017年8月17日
著者	Stefan Schoebel / Wei Mi / Alexander Stein / Sergey Ovchinnikov / Ryan Pavlovicz / Frank DiMaio / David Baker / Melissa G Chambers / Huayou Su / Dongsheng Li / Tom A Rapoport / Maofu Liao /
PubMed 要旨	Misfolded endoplasmic reticulum proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the membrane, and degraded by the proteasome-a ...Misfolded endoplasmic reticulum proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the membrane, and degraded by the proteasome-a pathway termed endoplasmic reticulum-associated protein degradation (ERAD). Proteins with misfolded domains in the endoplasmic reticulum lumen or membrane are discarded through the ERAD-L and ERAD-M pathways, respectively. In Saccharomyces cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain. Hrd1 is the crucial membrane component for retro-translocation, but it is unclear whether it forms a protein-conducting channel. Here we present a cryo-electron microscopy structure of S. cerevisiae Hrd1 in complex with its endoplasmic reticulum luminal binding partner, Hrd3. Hrd1 forms a dimer within the membrane with one or two Hrd3 molecules associated at its luminal side. Each Hrd1 molecule has eight transmembrane segments, five of which form an aqueous cavity extending from the cytosol almost to the endoplasmic reticulum lumen, while a segment of the neighbouring Hrd1 molecule forms a lateral seal. The aqueous cavity and lateral gate are reminiscent of features of protein-conducting conduits that facilitate polypeptide movement in the opposite direction-from the cytosol into or across membranes. Our results suggest that Hrd1 forms a retro-translocation channel for the movement of misfolded polypeptides through the endoplasmic reticulum membrane.
リンク	Nature / PubMed:28682307 / PubMed Central
手法	EM (単粒子)
解像度	3.9 - 4.7 Å
構造データ	8637 5v6p EMDB-8637, PDB-5v6p: CryoEM structure of the ERAD-associated E3 ubiquitin-protein ligase HRD1 手法: EM (単粒子) / 解像度: 4.1 Å EMDB-8638: Cryo-EM map of the ERAD components Hrd1/Hrd3 dimer 手法: EM (単粒子) / 解像度: 4.7 Å EMDB-8639: CryoEM map of Hrd1 dimer with one Hrd3 molecule 手法: EM (単粒子) / 解像度: 4.7 Å 8642 5v7v EMDB-8642, PDB-5v7v: Cryo-EM structure of ERAD-associated E3 ubiquitin-protein ligase component HRD3 手法: EM (単粒子) / 解像度: 3.9 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	Saccharomyces cerevisiae S288c (パン酵母) saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母)
キーワード	TRANSFERASE (転移酵素) / Retrotranslocon / E3 ligase (ユビキチンリガーゼ) / ERAD / PROTEIN TRANSPORT / Hrd3 ERAD