Clp is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin []and is a member of peptidase family S14. It exists as a heterodimer of ATP-binding regulatory A and catalytic P subunits, both of which are required for effective levels of protease activity in the presence of ATP [, ], although the P subunit alone does possess some catalytic activity []. This entry represents the P subunit.Proteases highly similar to ClpP have been found to be encoded in the genomeof bacteria, metazoa, some viruses and in the chloroplast of plants, but seems to be absent in archaea, mollicutes and some fungi []. Clp proteases are involved in a number of cellular processes such as degradation of misfolded proteins, regulation of short-lived proteins and housekeeping removal of dysfunctional proteins. They are also implicated in the control of cell growth, targeting DNA-binding protein from starved cells. ClpP has also been linked to the tight regulation of virulence genes in the pathogens Listeria monocytogenes and Salmonella typhimurium []. Active site consists of the triad Ser, His and Asp []; some members have lost all of these active site residues and are therefore inactive, while others may have one or two large insertions. ClpP seems to prefer hydrophobic or non-polar residues at P1 or P1' positions in its substrate. The protease exists as a tetradecamer made up of two heptameric rings stacked back-to-back such that the catalytic triad of each subunit is located at the interface between three monomers, thus making oligomerization essential for function [, ].
This entry corresponds to the C-terminal dimerization domain of CtsR. CtsR of L. monocytogenes negatively regulates the clpC, clpP and clpE genes belonging to the CtsR regulon [].
This family consists of several Firmicute transcriptional repressor of class III stress genes (CtsR) proteins. CtsR of L. monocytogenes negatively regulates the clpC, clpP and clpE genes belonging to the CtsR regulon []. This entry is the N-terminal HTH domain.
This family consists of several transcriptional repressor of class III stress gene (CtsR) proteins, mainly from Firmicute species. CtsR of Listeria monocytogenes negatively regulates the clpC, clpP and clpE genes belonging to the CtsR regulon [].
This family of archaebacterial proteins, formerly known as DUF114, has been found to be a serine dehydrogenase proteinase distantly related to ClpP proteinases that belong to the serine proteinase superfamily. The family belong to MEROPS peptidase family S49; they are mostly unassigned peptidases but include the archaean signal peptide peptidase 1 []. The family has a catalytic triad of Ser, Asp, His residues, which shows an altered residue ordering compared with the ClpP proteinases but similar to that of the carboxypeptidase clan [].
This entry includes peptidases from the MEROPS peptidase family S14, including ClpP endopeptidase and translocation-enhancing protein TepA.ClpP is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin []. It exists as a heterodimer of ATP-binding regulatory A and catalytic P subunits, both of which are required for effective levels of protease activity in the presence ofATP [], although the P subunit alone does possess some catalytic activity. Proteases highly similar to ClpP have been found to be encoded in the genome of bacteria, metazoa, some viruses and in the chloroplast of plants. A number of the proteins in this family are classified as non-peptidase homologues as they have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for catalytic activity. Translocation-enhancing protein TepA displays sequence similarity to ClpP. It is required for efficient translocation of pre-proteins across the membrane [].
The endopeptidase Clp () from Escherichia coli cleaves peptides invarious proteins in a process that requires ATP hydrolysis [, ]. Clp is adimeric protein which consists of a proteolytic subunit (gene clpP) and eitherof two related ATP-binding regulatory subunits (genes clpA and clpX). ClpP isa serine protease which has a chymotrypsin-like activity. Its catalyticactivity seems to be provided by a charge relay system similar to that of thetrypsin family of serine proteases, but which evolved by independentconvergent evolution.Proteases highly similar to ClpP have been found to be encoded in the genomeof the chloroplast of plants and seem to be also present in other eukaryotes.This entry represents a conserved region containing a histidine that is involved in the catalytic triad.
This superfamily represents the N-terminal winged HTH domain of CtsR, a dimeric repressor. The members include several Firmicute transcriptional repressor of class III stress genes (CtsR) proteins. CtsR of L. monocytogenes negatively regulates the clpC, clpP and clpE genes belonging to the CtsR regulon [].CtsR consists of an N-terminal domain, a DNA binding domain with a helix-turn-helix motif (HTH) and a C-terminal dimerisation domain organised in a four helix bundle, with an unknown function. CtsR has a role in forming a complex with DNA, binding to promoter regions of heat-shock genes. It is mainly involved in the regulatory network of the bacterial heat-shock response. The phosphorylation sites reside in the winged HTH domain [].
Proteins in this entry are related to ClpA () from Escherichia coli. ClpA is an ATP-dependent chaperone and part of the ClpAP protease that participates in regulatory protein degradation and the dissolution and degradation of protein aggregates []. ClpA functions as the regulatory component of the ATP dependent protease complex ClpAP []. ClpA recognises sequences in specific proteins, which it then unfolds in an ATP-dependent manner and transports into the degradation chamber of the associated ClpP protease [, ]. A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein []. It protects ClpA from autodegradation and appears to redirect its activity away from soluble proteins and toward aggregated proteins.
Clp is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin []. It exists as a heterodimer of ATP-binding regulatory A and catalytic P subunits, both of which are required for effective levels of protease activity in the presence ofATP [], although the P subunit alone does possess some catalytic activity.Proteases highly similar to ClpP have been found to be encoded in the genomeof bacteria, metazoa, some viruses and in the chloroplast of plants. A number of the proteins in this family are classified as non-peptidase homologues as they have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for catalytic activity.This entry represents a conserved region containing a serine that is involved in the catalytic triad.
ClpA is an ATP-dependent chaperone and part of the ClpAP protease that participates in regulatory protein degradation and the dissolution and degradation of protein aggregates []. ClpA recognises sequences in specific proteins, which it then unfolds in an ATP-dependent manner and transports into the degradation chamber of the associated ClpP protein [, ]. A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein []. It protects ClpA from autodegradation and appears to redirect its activity away from soluble proteins and toward aggregated proteins.Molecular chaperones recognize unfolded or misfolded proteins by binding to hydrophobic surface patches not normally exposed in the native proteins. Members of the Clp/Hsp100 family of chaperones are present in eubacteria and within organelles of all eukaryotes, promoting disaggregation and disassembly of protein complexes and participating in energy-dependent protein degradation. The ClpA, ClpB, and ClpC subfamilies of the Clp/Hsp100 ATPases contain a conserved N-terminal domain of ~150 amino acids, which in turn consists of two repeats of ~75 residues. Although the Clp repeat (R) domain contains two approximate sequence repeats, it behaves as a single cooperatively folded unit. The Clp R domain is thought to provide a means for regulating the specificity of and to enlarge the substrate pool available to Clp/Hsp100 chaperone or protease complexes. These roles can be assisted through the binding of an adaptor protein. Adaptor proteins bind to the Clp R domain, modulate the target specificity of the Clp/Hsp100 complex to a particular substrate of interest, and may also regulate the activity of the complex [, , , , , ].The Clp R domain is monomeric and partially alpha helical. It is a single folding unit with pseudo 2-fold symmetry. The Clp R domain structure consists of two four-helix bundles connected by a flexible loop [, , ]. This entry represents the Clp repeat (R) domain [].
