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-Structure paper
タイトル | Structural insights into ClpP protease side exit pore-opening by a pH drop coupled with substrate hydrolysis. |
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ジャーナル・号・ページ | EMBO J, Vol. 41, Issue 13, Page e109755, Year 2022 |
掲載日 | 2022年7月4日 |
著者 | Leehyeon Kim / Byung-Gil Lee / Minki Kim / Min Kyung Kim / Do Hoon Kwon / Hyunmin Kim / Heike Brötz-Oesterhelt / Soung-Hun Roh / Hyun Kyu Song / |
PubMed 要旨 | 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. ...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. |
リンク | EMBO J / PubMed:35593068 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.79 - 3.4 Å |
構造データ | EMDB-31559, PDB-7fep: EMDB-31560, PDB-7feq: EMDB-31561, PDB-7fer: EMDB-31562, PDB-7fes: PDB-7p80: PDB-7p81: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | HYDROLASE / ClpP / Bacillus subtilis / ADEP1 / Acyldepsipeptides / ADEP2 / compressed / antibiotics |