Structural insights into the conformational diversity of ClpP from Bacillus subtilis

Byung Gil Lee, Min Kyung Kim, Hyun Kyu Song

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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 activators 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 compressed forms of ClpP from B. subtilis is available. Structural 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.

Original languageEnglish
Pages (from-to)589-595
Number of pages7
JournalMolecules and cells
Volume32
Issue number6
DOIs
Publication statusPublished - 2011 Dec

Keywords

  • Bacillus
  • ClpP
  • Clpxp
  • Proteasome
  • Side pore

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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