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Structure paper

タイトル	Substrate-engaged 26 proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation.
ジャーナル・号・ページ	Science, Vol. 362, Issue 6418, Year 2018
掲載日	2018年11月30日
著者	Andres H de la Peña / Ellen A Goodall / Stephanie N Gates / Gabriel C Lander / Andreas Martin /
PubMed 要旨	The 26 proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the ...The 26 proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-electron microscopy structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26 proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination and how ATP-binding, -hydrolysis, and phosphate-release events are coordinated within the AAA+ (ATPases associated with diverse cellular activities) motor to induce conformational changes and propel the substrate through the central pore.
リンク	Science / PubMed:30309908 / PubMed Central
手法	EM (単粒子)
解像度	4.17 - 4.73 Å
構造データ	9042 6ef0 EMDB-9042, PDB-6ef0: Yeast 26S proteasome bound to ubiquitinated substrate (1D* motor state) 手法: EM (単粒子) / 解像度: 4.43 Å 9043 6ef1 EMDB-9043, PDB-6ef1: Yeast 26S proteasome bound to ubiquitinated substrate (5D motor state) 手法: EM (単粒子) / 解像度: 4.73 Å 9044 6ef2 EMDB-9044, PDB-6ef2: Yeast 26S proteasome bound to ubiquitinated substrate (5T motor state) 手法: EM (単粒子) / 解像度: 4.27 Å 9045 6ef3 EMDB-9045, PDB-6ef3: Yeast 26S proteasome bound to ubiquitinated substrate (4D motor state) 手法: EM (単粒子) / 解像度: 4.17 Å
化合物	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM / アデノシン二リン酸 ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸
由来	saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母) homo sapiens (ヒト) saccharomyces cerevisiae s288c (パン酵母)
キーワード	MOTOR PROTEIN (モータータンパク質) / 26S Proteasome (プロテアソーム) / ATPase (ATPアーゼ) / AAA+ / Protease (プロテアーゼ) / Ubiquitin (ユビキチン)