InterPro domain: IPR036628

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 [ 1 ]. 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 [ 2 , 3 ]. A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein [ 4 ]. 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 [ 5 , 6 , 7 , 8 , 9 , 10 ].

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 [ 11 , 11 , 11 ].

This entry represents the Clp repeat (R) domain [ 11 ].

1. The ATP-dependent Clp protease of Escherichia coli. Sequence of clpA and identification of a Clp-specific substrate. J. Biol. Chem. 265, 7886-93
2. Global unfolding of a substrate protein by the Hsp100 chaperone ClpA. Nature 401, 90-3
3. Translocation pathway of protein substrates in ClpAP protease. Proc. Natl. Acad. Sci. U.S.A. 98, 4328-33
4. Crystal structure of the heterodimeric complex of the adaptor, ClpS, with the N-domain of the AAA+ chaperone, ClpA. J. Biol. Chem. 277, 46753-62
5. Characterization of the N-terminal repeat domain of Escherichia coli ClpA-A class I Clp/HSP100 ATPase. Protein Sci. 10, 551-9
6. Crystallographic investigation of peptide binding sites in the N-domain of the ClpA chaperone. J. Struct. Biol. 146, 166-79
7. Crystal structures of Hsp104 N-terminal domains from Saccharomyces cerevisiae and Candida albicans suggest the mechanism for the function of Hsp104 in dissolving prions. Acta Crystallogr D Struct Biol 73, 365-372
8. Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions. J. Mol. Biol. 387, 639-52
9. Structures, Functions, and Interactions of ClpT1 and ClpT2 in the Clp Protease System of Arabidopsis Chloroplasts. Plant Cell 27, 1477-96
10. SMAX1-LIKE7 Signals from the Nucleus to Regulate Shoot Development in Arabidopsis via Partially EAR Motif-Independent Mechanisms. Plant Cell 28, 1581-601
11. Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease. J. Biol. Chem. 277, 46743-52