9CC3

Human Mitochondrial LONP1 Stall State + casein

9CC3 の概要

• エントリーDOI: 10.2210/pdb9cc3/pdb
• EMDBエントリー: 45433
• 分子名称: Endogenous Co-purified substrate modeled as unknown residues, Lon protease homolog, mitochondrial, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: atpase, protease, hydrolase
• 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: 589186.12

構造登録者

Mindrebo, J.T.,Lander, G.C. (登録日: 2024-06-20, 公開日: 2024-08-07)

主引用文献

Mindrebo, J.T.,Lander, G.C.
Structural and mechanistic studies on human LONP1 redefine the hand-over-hand translocation mechanism.
Biorxiv, 2024

PubMed Abstract: AAA+ enzymes use energy from ATP hydrolysis to remodel diverse cellular targets. Structures of substrate-bound AAA+ complexes suggest that these enzymes employ a conserved hand-over-hand mechanism to thread substrates through their central pore. However, the fundamental aspects of the mechanisms governing motor function and substrate processing within specific AAA+ families remain unresolved. We used cryo-electron microscopy to structurally interrogate reaction intermediates from in vitro biochemical assays to inform the underlying regulatory mechanisms of the human mitochondrial AAA+ protease, LONP1. Our results demonstrate that substrate binding allosterically regulates proteolytic activity, and that LONP1 can adopt a configuration conducive to substrate translocation even when the ATPases are bound to ADP. These results challenge the conventional understanding of the hand-over-hand translocation mechanism, giving rise to an alternative model that aligns more closely with biochemical and biophysical data on related enzymes like ClpX, ClpA, the 26S proteasome, and Lon protease.

PubMed: 38979310
DOI: 10.1101/2024.06.24.600538

実験手法

ELECTRON MICROSCOPY (3.23 Å)