Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism

Byung Gil Lee, Eun Young Park, Kyung Eun Lee, Hyesung Jeon, Kwang Hoon Sung, Holger Paulsen, Helga Rübsamen-Schaeff, Heike Brötz-Oesterhelt, Hyun Kyu Song

Research output: Contribution to journalArticle

127 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalNature Structural and Molecular Biology
Volume17
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1

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ATP-Dependent Proteases
Anti-Bacterial Agents
Bacillus subtilis
Cluster Analysis
Adenosine Triphosphatases
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. / Lee, Byung Gil; Park, Eun Young; Lee, Kyung Eun; Jeon, Hyesung; Sung, Kwang Hoon; Paulsen, Holger; Rübsamen-Schaeff, Helga; Brötz-Oesterhelt, Heike; Song, Hyun Kyu.

In: Nature Structural and Molecular Biology, Vol. 17, No. 4, 01.04.2010, p. 471-478.

Research output: Contribution to journalArticle

Lee, BG, Park, EY, Lee, KE, Jeon, H, Sung, KH, Paulsen, H, Rübsamen-Schaeff, H, Brötz-Oesterhelt, H & Song, HK 2010, 'Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism', Nature Structural and Molecular Biology, vol. 17, no. 4, pp. 471-478. https://doi.org/10.1038/nsmb.1787
Lee, Byung Gil ; Park, Eun Young ; Lee, Kyung Eun ; Jeon, Hyesung ; Sung, Kwang Hoon ; Paulsen, Holger ; Rübsamen-Schaeff, Helga ; Brötz-Oesterhelt, Heike ; Song, Hyun Kyu. / Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 4. pp. 471-478.
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