Structure and mechanism of the caseinolytic protease ClpP1/2 heterocomplex from Listeria monocytogenes

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Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
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Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes

Published on: September 19, 2013

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Maria Dahmen1, Marie-Theres Vielberg, Michael Groll

  • 1Center for Integrated Protein Science Munich CIPSM, Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching (Germany).

Angewandte Chemie (International Ed. in English)
|January 30, 2015
PubMed

Insights

Listeria monocytogenes uses two distinct caseinolytic protease P (ClpP) enzymes. Their structural interlocking forms a tetradecamer, enhancing proteolytic activity crucial for bacterial virulence and stress tolerance.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • Listeria monocytogenes is a significant bacterial pathogen.
  • Its virulence and intracellular stress tolerance depend on caseinolytic protease P (ClpP).
  • L. monocytogenes possesses two distinct ClpP isoforms with differing catalytic and structural properties.

Purpose of the Study:

  • To elucidate the structural and functional characteristics of the L. monocytogenes ClpP1/2 heterocomplex.
  • To understand the mechanism by which ClpP contributes to bacterial virulence and stress adaptation.

Main Methods:

  • X-ray crystallography to determine the heterocomplex structure.
  • Biochemical assays to assess proteolytic activity and stability.

Main Results:

  • The crystal structure of the LmClpP1/2 heterocomplex was solved, revealing a tetradecameric assembly.
  • Structural interlocking of LmClpP1 and LmClpP2 aligns all 14 active sites.
  • This arrangement significantly enhances proteolytic activity and confers transient stability to the enzyme complex.

Conclusions:

  • The L. monocytogenes ClpP1/2 tetradecamer is a key functional unit.
  • The specific structural interactions between isoforms are critical for enhanced enzymatic activity.
  • Understanding ClpP function provides insights into bacterial pathogenesis and potential therapeutic targets.
Keywords:
ClpPenzyme catalysisheterocomplexesprotein structuresproteolysis

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