Lee, Byung-Gil Park, Eun Young Lee, Kyung-Eun Jeon, Hyesung Sung, Kwang Hoon Paulsen, Holger Ruebsamen-Schaeff, Helga Broetz-Oesterhelt, Heike Song, Hyun Kyu 2024-01-20T19:32:57Z 2024-01-20T19:32:57Z 2021-09-02 2010-04 1545-9993 https://pubs.kist.re.kr/handle/201004/131582 Clp-family proteins are prototypes for studying the mechanism of ATP-dependent proteases because the proteolytic activity of the ClpP core is tightly regulated by activating Clp-ATPases. Nonetheless, the proteolytic activation mechanism has remained elusive because of the lack of a complex structure. Acyldepsipeptides (ADEPs), a recently discovered class of antibiotics, activate and disregulate ClpP. Here we have elucidated the structural changes underlying the ClpP activation process by ADEPs. We present the structures of Bacillus subtilis ClpP alone and in complex with ADEP1 and ADEP2. The structures show the closed-to-open-gate transition of the ClpP N-terminal segments upon activation as well as conformational changes restricted to the upper portion of ClpP. The direction of the conformational movement and the hydrophobic clustering that stabilizes the closed structure are markedly different from those of other ATP-dependent proteases, providing unprecedented insights into the activation of ClpP. English NATURE PUBLISHING GROUP CRYSTAL-STRUCTURE 20S PROTEASOME ESCHERICHIA-COLI RECOGNITION PROTEOLYSIS INHIBITOR ATPASES GATE CRYSTALLOGRAPHY COMMUNICATION Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism Article 10.1038/nsmb.1787 1 NATURE STRUCTURAL & MOLECULAR BIOLOGY, v.17, no.4, pp.471 - U116 NATURE STRUCTURAL & MOLECULAR BIOLOGY 17 4 471 U116 scie scopus 000276416800016 2-s2.0-77950519954 Biochemistry & Molecular Biology Biophysics Cell Biology Biochemistry & Molecular Biology Biophysics Cell Biology Article CRYSTAL-STRUCTURE 20S PROTEASOME ESCHERICHIA-COLI RECOGNITION PROTEOLYSIS INHIBITOR ATPASES GATE CRYSTALLOGRAPHY COMMUNICATION