7NGF

P2c-state of wild type human mitochondrial LONP1 protease with bound endogenous substrate protein and in presence of ATP/ADP mix

7NGF の概要

• エントリーDOI: 10.2210/pdb7ngf/pdb
• 関連するPDBエントリー: 7NFY 7NG4 7NG5 7NGC 7NGL 7NGP 7NGQ 7OWA
• EMDBエントリー: 12307 12308 12312 12313 12315 12316 12317
• 分子名称: Lon protease homolog, mitochondrial, substrate protein chain:G, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: human mitochondrial aaa+ protease, motor protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 566991.71

構造登録者

Mohammed, I.,Schmitz, K.A.,Schenck, N.,Maier, T.,Abrahams, J.P. (登録日: 2021-02-09, 公開日: 2021-04-28, 最終更新日: 2025-07-09)

主引用文献

Mohammed, I.,Schmitz, K.A.,Schenck, N.,Balasopoulos, D.,Topitsch, A.,Maier, T.,Abrahams, J.P.
Catalytic cycling of human mitochondrial Lon protease.
Structure, 30:1254-1268.e7, 2022

PubMed Abstract: The mitochondrial Lon protease (LonP1) regulates mitochondrial health by removing redundant proteins from the mitochondrial matrix. We determined LonP1 in eight nucleotide-dependent conformational states by cryoelectron microscopy (cryo-EM). The flexible assembly of N-terminal domains had 3-fold symmetry, and its orientation depended on the conformational state. We show that a conserved structural motif around T803 with a high similarity to the trypsin catalytic triad is essential for proteolysis. We show that LonP1 is not regulated by redox potential, despite the presence of two conserved cysteines at disulfide-bonding distance in its unfoldase core. Our data indicate how sequential ATP hydrolysis controls substrate protein translocation in a 6-fold binding change mechanism. Substrate protein translocation, rather than ATP hydrolysis, is a rate-limiting step, suggesting that LonP1 is a Brownian ratchet with ATP hydrolysis preventing translocation reversal. 3-fold rocking motions of the flexible N-domain assembly may assist thermal unfolding of the substrate protein.

PubMed: 35870450
DOI: 10.1016/j.str.2022.06.006

実験手法

ELECTRON MICROSCOPY (5.6 Å)