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Mol. Cells 2011; 32(6): 589-595

Published online December 31, 2011

https://doi.org/10.1007/s10059-011-0197-1

© The Korean Society for Molecular and Cellular Biology

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Byung-Gil Lee, Min Kyung Kim, and Hyun Kyu Song*

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea

Correspondence to : *Correspondence: hksong@korea.ac.kr

Received: September 17, 2011; Revised: October 11, 2011; Accepted: October 12, 2011

Abstract

ClpP is a cylindrical protease that is tightly regulated by Clp-ATPases. The activation mechanism of ClpP using acyldepsipeptide antibiotics as mimics of natural activa-tors showed enlargement of the axial entrance pore for easier processing of incoming substrates. However, the elimination of degradation products from inside the ClpP chamber remains unclear since there is no exit pore for releasing these products in all determined ClpP structures. Here we report a new crystal structure of ClpP from Bacillus subtilis, which shows a significantly compressed shape along the axial direction. A portion of the handle regions comprising the heptameric ring-ring contacts shows structural transition from an ordered to a disordered state, which triggers the large conformational change from an extended to an overall compressed structure. Along with this structural change, 14 side pores are generated for product release and the catalytic triad adopts an inactive orientation. We have also determined B. subtilis ClpP inhibited by diisopropylfluoro-phosphate and analyzed the active site in detail. Structural information pertaining to several different conformational steps such as those related to extended, ADEP-activated, DFP-inhibited and com-pressed forms of ClpP from B. subtilis is available. Struc-tural comparisons suggest that functionally important regions in the ClpP-family such as N-terminal segments for the axial pore, catalytic triads, and handle domains for the product releasing pore exhibit intrinsically dynamic and unique structural features. This study provides valuable insights for understanding the enigmatic cylindrical degradation machinery of ClpP as well as other related proteases such as HslV and the 20S proteasome.

Keywords Bacillus, ClpP, ClpXP, proteasome, side pore

Article

Research Article

Mol. Cells 2011; 32(6): 589-595

Published online December 31, 2011 https://doi.org/10.1007/s10059-011-0197-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Byung-Gil Lee, Min Kyung Kim, and Hyun Kyu Song*

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea

Correspondence to:*Correspondence: hksong@korea.ac.kr

Received: September 17, 2011; Revised: October 11, 2011; Accepted: October 12, 2011

Abstract

ClpP is a cylindrical protease that is tightly regulated by Clp-ATPases. The activation mechanism of ClpP using acyldepsipeptide antibiotics as mimics of natural activa-tors showed enlargement of the axial entrance pore for easier processing of incoming substrates. However, the elimination of degradation products from inside the ClpP chamber remains unclear since there is no exit pore for releasing these products in all determined ClpP structures. Here we report a new crystal structure of ClpP from Bacillus subtilis, which shows a significantly compressed shape along the axial direction. A portion of the handle regions comprising the heptameric ring-ring contacts shows structural transition from an ordered to a disordered state, which triggers the large conformational change from an extended to an overall compressed structure. Along with this structural change, 14 side pores are generated for product release and the catalytic triad adopts an inactive orientation. We have also determined B. subtilis ClpP inhibited by diisopropylfluoro-phosphate and analyzed the active site in detail. Structural information pertaining to several different conformational steps such as those related to extended, ADEP-activated, DFP-inhibited and com-pressed forms of ClpP from B. subtilis is available. Struc-tural comparisons suggest that functionally important regions in the ClpP-family such as N-terminal segments for the axial pore, catalytic triads, and handle domains for the product releasing pore exhibit intrinsically dynamic and unique structural features. This study provides valuable insights for understanding the enigmatic cylindrical degradation machinery of ClpP as well as other related proteases such as HslV and the 20S proteasome.

Keywords: Bacillus, ClpP, ClpXP, proteasome, side pore

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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