4JCQ

ClpP1 from Listeria monocytogenes

Summary for 4JCQ

• Entry DOI: 10.2210/pdb4jcq/pdb
• Related: 1TYF 2FZS 3V5E 4JCR
• Descriptor: ATP-dependent Clp protease proteolytic subunit (2 entities in total)
• Functional Keywords: pathogenic bacteria, virulence factor, regulation, clp protease family, inactive catalytic triad, hydrolase
• Biological source: Listeria monocytogenes
• Cellular location: Cytoplasm (By similarity): Q8Y7Y1
• Total number of polymer chains: 28
• Total formula weight: 635645.22

Authors

Zeiler, E.,List, A.,Alte, F.,Gersch, M.,Wachtel, R.,Groll, M.,Sieber, S. (deposition date: 2013-02-22, release date: 2013-06-12, Last modification date: 2023-09-20)

Primary citation

Zeiler, E.,List, A.,Alte, F.,Gersch, M.,Wachtel, R.,Poreba, M.,Drag, M.,Groll, M.,Sieber, S.A.
Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad.
Proc.Natl.Acad.Sci.USA, 110:11302-11307, 2013

PubMed Abstract: Caseinolytic proteases (ClpPs) are large oligomeric protein complexes that contribute to cell homeostasis as well as virulence regulation in bacteria. Although most organisms possess a single ClpP protein, some organisms encode two or more ClpP isoforms. Here, we elucidated the crystal structures of ClpP1 and ClpP2 from pathogenic Listeria monocytogenes and observe an unprecedented regulation principle by the catalytic triad. Whereas L. monocytogenes (Lm)ClpP2 is both structurally and functionally similar to previously studied tetradecameric ClpP proteins from Escherichia coli and Staphylococcus aureus, heptameric LmClpP1 features an asparagine in its catalytic triad. Mutation of this asparagine to aspartate increased the reactivity of the active site and led to the assembly of a tetradecameric complex. We analyzed the heterooligomeric complex of LmClpP1 and LmClpP2 via coexpression and subsequent labeling studies with natural product-derived probes. Notably, the LmClpP1 peptidase activity is stimulated 75-fold in the complex providing insights into heterooligomerization as a regulatory mechanism. Collectively, our data point toward different preferences for substrates and inhibitors of the two ClpP enzymes and highlight their structural and functional characteristics.

PubMed: 23798410
DOI: 10.1073/pnas.1219125110

Experimental method

X-RAY DIFFRACTION (2 Å)