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- Title
Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism.
- Authors
Byung-Gil Lee; Eun Young Park; Kyung-Eun Lee; Hyesung Jeon; Kwang Hoon Sung; Paulsen, Holger; Rübsamen-Schaeff, Helga; Brötz-Oesterhelt, Heike; Hyun Kyu Song
- Abstract
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.
- Subjects
ANTIBIOTICS; PROTEINS; MICROBIAL metabolites; BACILLUS subtilis; PROTEOLYTIC enzymes
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 4, p471
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1787