7FER

Cryo-EM structure of BsClpP-ADEP1 complex at pH 4.2

7FER の概要

• エントリーDOI: 10.2210/pdb7fer/pdb
• EMDBエントリー: 31561
• 関連するBIRD辞書のPRD_ID: PRD_000503
• 分子名称: ATP-dependent Clp protease proteolytic subunit, ADEP1 (2 entities in total)
• 機能のキーワード: clpp, bacillus subtilis, hydrolase, adep1
• 由来する生物種: Bacillus subtilis; 詳細
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 323981.27

構造登録者

Kim, L.,Lee, B.-G.,Kim, M.K.,Kwon, D.H.,Kim, H.,Brotz-Oesterhelt, H.,Roh, S.-H.,Song, H.K. (登録日: 2021-07-21, 公開日: 2022-07-06, 最終更新日: 2022-07-20)

主引用文献

Kim, L.,Lee, B.G.,Kim, M.,Kim, M.K.,Kwon, D.H.,Kim, H.,Brotz-Oesterhelt, H.,Roh, S.H.,Song, H.K.
Structural insights into ClpP protease side exit pore-opening by a pH drop coupled with substrate hydrolysis.
Embo J., 41:e109755-e109755, 2022

PubMed Abstract: The ClpP serine peptidase is a tetradecameric degradation molecular machine involved in many physiological processes. It becomes a competent ATP-dependent protease when coupled with Clp-ATPases. Small chemical compounds, acyldepsipeptides (ADEPs), are known to cause the dysregulation and activation of ClpP without ATPases and have potential as novel antibiotics. Previously, structural studies of ClpP from various species revealed its structural details, conformational changes, and activation mechanism. Although product release through side exit pores has been proposed, the detailed driving force for product release remains elusive. Herein, we report crystal structures of ClpP from Bacillus subtilis (BsClpP) in unforeseen ADEP-bound states. Cryo-electron microscopy structures of BsClpP revealed various conformational states under different pH conditions. To understand the conformational change required for product release, we investigated the relationship between substrate hydrolysis and the pH-lowering process. The production of hydrolyzed peptides from acidic and basic substrates by proteinase K and BsClpP lowered the pH values. Our data, together with those of previous findings, provide insight into the molecular mechanism of product release by the ClpP self-compartmentalizing protease.

PubMed: 35593068
DOI: 10.15252/embj.2021109755

実験手法

ELECTRON MICROSCOPY (3.4 Å)