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 language | English |
|---|---|
| Pages (from-to) | 471-478 |
| Number of pages | 8 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 17 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2010 Apr 1 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism
AU - Lee, Byung Gil
AU - Park, Eun Young
AU - Lee, Kyung Eun
AU - Jeon, Hyesung
AU - Sung, Kwang Hoon
AU - Paulsen, Holger
AU - Rübsamen-Schaeff, Helga
AU - Brötz-Oesterhelt, Heike
AU - Song, Hyun Kyu
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77950519954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950519954&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1787
DO - 10.1038/nsmb.1787
M3 - Article
C2 - 20305655
AN - SCOPUS:77950519954
VL - 17
SP - 471
EP - 478
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 4
ER -