D-peptide ligands for the co-chaperone DnaJ
- PMID: 9575139
- DOI: 10.1074/jbc.273.20.11999
D-peptide ligands for the co-chaperone DnaJ
Abstract
The molecular chaperone DnaK, the Hsp70 homolog of Escherichia coli, binds hydrophobic polypeptide segments in extended conformation. The co-chaperone DnaJ (Hsp40) has been reported to bind native and denatured proteins as well as peptides. We tested pseudo-peptides of D-amino acids as ligands for both chaperones. In comparison to the parent all-L peptide, these mimetics had either enantiomorphic side chain positions combined with retained main chain direction (normal all-D peptide) or unchanged side chain topology together with reverse direction of the peptide backbone (retro all-D peptide). The peptides were labeled with acrylodan (a), and their binding to DnaK and DnaJ was monitored by the accompanying increase in fluorescence intensity. The parent all-L peptide a-CALLLSAARR bound to both DnaK (Kd = 0.1 microM) and DnaJ (Kd = 9.2 microM). In contrast, the normal all-D and retro all-D peptides did not bind to DnaK; they bound, however, to DnaJ with Kd values of 6.8 microM and 0.9 microM, respectively. The emission spectra of the DnaJ-bound peptides suggests that DnaJ bound both D-peptides with the same main chain direction as L-peptides. Binding of the normal all-D and all-L peptides inhibited the DnaJ-induced stimulation of DnaK ATPase. However, binding of the retro all-D analog to DnaJ did not impair the stimulation, indicating the existence of separate binding sites for peptides and DnaK.
Similar articles
-
D-Peptides as inhibitors of the DnaK/DnaJ/GrpE chaperone system.J Biol Chem. 2003 May 23;278(21):19044-7. doi: 10.1074/jbc.M300922200. Epub 2003 Mar 10. J Biol Chem. 2003. PMID: 12637539
-
The power stroke of the DnaK/DnaJ/GrpE molecular chaperone system.J Mol Biol. 1997 Jun 27;269(5):757-68. doi: 10.1006/jmbi.1997.1072. J Mol Biol. 1997. PMID: 9223639
-
Mechanism of the targeting action of DnaJ in the DnaK molecular chaperone system.J Biol Chem. 2003 May 23;278(21):19038-43. doi: 10.1074/jbc.M300756200. Epub 2003 Mar 24. J Biol Chem. 2003. PMID: 12654915
-
Putting human Tid-1 in context: an insight into its role in the cell and in different disease states.Cell Commun Signal. 2022 Jul 19;20(1):109. doi: 10.1186/s12964-022-00912-5. Cell Commun Signal. 2022. PMID: 35854300 Free PMC article. Review.
-
Multi-faceted role of HSP40 in cancer.Clin Exp Metastasis. 2009;26(6):559-67. doi: 10.1007/s10585-009-9255-x. Epub 2009 Apr 2. Clin Exp Metastasis. 2009. PMID: 19340594 Review.
Cited by
-
Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone.EMBO J. 2001 Mar 1;20(5):1042-50. doi: 10.1093/emboj/20.5.1042. EMBO J. 2001. PMID: 11230128 Free PMC article.
-
Hsp70 protein complexes as drug targets.Curr Pharm Des. 2013;19(3):404-17. doi: 10.2174/138161213804143699. Curr Pharm Des. 2013. PMID: 22920901 Free PMC article. Review.
-
Allostery in the Hsp70 chaperone proteins.Top Curr Chem. 2013;328:99-153. doi: 10.1007/128_2012_323. Top Curr Chem. 2013. PMID: 22576356 Free PMC article. Review.
-
L and D presequence peptides derived from the precursor of F1beta subunit of the ATP synthase inhibit mitochondrial protein import by interaction with import machinery.Plant Mol Biol. 2001 Dec;47(6):815-26. doi: 10.1023/a:1013639330716. Plant Mol Biol. 2001. PMID: 11785942
-
Peptide substrate identification for yeast Hsp40 Ydj1 by screening the phage display library.Biol Proced Online. 2004;6:204-208. doi: 10.1251/bpo90. Epub 2004 Oct 1. Biol Proced Online. 2004. PMID: 15472720 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
