PMID:9987112

Citation	Frees, D and Ingmer, H (1999) ClpP participates in the degradation of misfolded protein in Lactococcus lactis. Mol. Microbiol. 31:79-87
Abstract	ClpP proteins constitute a family of homologous proteins found in both prokaryotic and eukaryotic organisms. In Escherichia coli, ClpP is the proteolytic component of a large complex also containing either the ClpA or the ClpX ATPases. We show here that the clpP gene from the Gram-positive bacterium Lactococcus lactis encodes a 22-kDa protein that is induced by low pH and by the t-RNA analogue puromycin, which interferes with translation, resulting in the production of misfolded puromycyl-containing peptides. Northern blot and primer extension analysis showed that clpP expression is also induced by heat shock and that stress induction occurs at the transcriptional level independent of the CIRCE regulatory element often implicated in stress regulation in Gram-positive bacteria. When we disrupted the L. lactis clpP gene by insertional inactivation, the resulting mutant was more sensitive to both heat and puromycin than wild-type cells. Furthermore, cells lacking ClpP had a reduced ability to degrade puromycyl-containing peptides, and they synthesized heat shock proteins constitutively in the absence of stress. Thus, our data suggest that ClpP plays a major role in the degradation of misfolded proteins.
Links	PubMed
Keywords	Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Amino Acid Sequence; Base Sequence; DNA, Bacterial; Drug Resistance, Microbial; Endopeptidase Clp; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Genes, Bacterial; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Heat-Shock Response; Lactococcus lactis/drug effects; Lactococcus lactis/genetics; Lactococcus lactis/metabolism; Molecular Chaperones; Molecular Sequence Data; Protein Folding; Protein Processing, Post-Translational; Puromycin/pharmacology; Sequence Analysis, DNA; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism; Transcription, Genetic
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
LACLM:CLPP	involved_in	GO:0006515: protein quality control for misfolded or incompletely synthesized proteins	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
LACLM:CLPP		GO:0006515: misfolded or incompletely synthesized protein catabolic process	ECO:0000315:		P		Figure 5 shows that a clpP mutant strain has a reduced ability to degrade puromycyl-containing polypeptides which are comparable to misfolded proteins. This indicates that ClpP degrades misfolded proteins.	complete CACAO 7695

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