Disease relevance of ECs0015

• In Escherichia coli, the heat-shock protein DnaJ and the Hsp70 homologue, DnaK, act together to disassemble a protein complex involved in bacteriophage lambda replication [1].
• Together, our findings suggest that TAg uses its J-domain to support SV40 DNA replication in a manner that is strikingly similar to the use of Escherichia coli DnaJ by bacteriophage lambda in DNA replication [2].
• The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone [3].
• These findings implicate hTid-1 in HSV-1 DNA replication, and suggest that this cellular protein may provide a chaperone function analogous to the DnaJ protein in Escherichia coli DNA replication [4].
• A novel factor required for the assembly of the DnaK and DnaJ chaperones of Thermus thermophilus [5].

High impact information on ECs0015

• Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding [6].
• A homologue of the bacterial heat-shock gene DnaJ that alters protein sorting in yeast [1].
• DnaK, DnaJ, and GrpE heat shock proteins negatively regulate heat shock gene expression by controlling the synthesis and stability of sigma 32 [7].
• A function for the QKRAA amino acid motif: mediating binding of DnaJ to DnaK. Implications for the association of rheumatoid arthritis with HLA-DR4 [8].
• The binding motif of DnaJ consists of a hydrophobic core of approximately eight residues enriched for aromatic and large aliphatic hydrophobic residues and arginine [9].

Chemical compound and disease context of ECs0015

• In this study, we address the function of the conserved glycine- and phenyalanine-rich (G/F-rich) region of the Escherichia coli DnaJ in the DnaK chaperone cycle [10].
• Solution structure of the cysteine-rich domain of the Escherichia coli chaperone protein DnaJ [11].
• NMR structure of the J-domain and the Gly/Phe-rich region of the Escherichia coli DnaJ chaperone [12].
• The recombinant N-terminal 107-amino acid polypeptide fragment 2-108 of the DnaJ molecular chaperone of Escherichia coli, which contains the J-domain (residues 2 to 76) and the Gly/Phe-rich region (residues 77 to 108), was uniformly labeled with nitrogen-15 and carbon-13 [12].
• The role of two chaperone proteins, DnaK and the cooperating factor DnaJ, in Escherichia coli antibiotic susceptibility to three antibiotics (a beta-lactam, chloramphenicol, tetracycline) has been studied [13].

Biological context of ECs0015

• DnaJ, through rapid association with sigma32 and stimulation of hydrolysis of DnaK-bound ATP, mediates efficient binding of DnaK to sigma32 in the presence of ATP, resulting in DnaK-DnaJ-sigma32 complexes containing ADP [14].
• Escherichia coli chaperones DnaJ, DnaK and GrpE increase P1 plasmid initiator binding to the origin by promoting initiator folding [15].
• These data indicate that reversible inhibition of sigma32 activity through transient association of DnaK and DnaJ is a central regulatory element of the heat shock response [14].
• Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone [9].
• We have obtained a cDNA clone from the higher plant Atriplex nummularia that encodes a 46.6-kD polypeptide (ANJ1) with an overall 35.2% amino acid sequence identity with the E. coli DnaJ [16].

Anatomical context of ECs0015

• A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein [17].
• Protein uptake into microsomes and mitochondria was also interrupted by DnaJ [18].
• The Escherichia coli Hsp40 DnaJ and Hsp70 DnaK cooperate in the binding of proteins at intermediate stages of folding, assembly, and translocation across membranes [19].
• DnaJ plus DnaK interacted with the peptide on the ribosome [20].
• DnaJ homologues have been identified in most organelles where they are involved in nearly all aspects of protein synthesis and folding [21].

Associations of ECs0015 with chemical compounds

• As demonstrated by atomic absorption and extended X-ray absorption fine structure spectroscopy (EXAFS), the 90 amino acid cysteine-rich region of DnaJ contains two Zn atoms tetrahedrally coordinated to four cysteine residues, resembling their arrangement in the C4 Zn binding domains of certain DNA binding proteins [22].
• This DnaJ-sigma 32-DnaK complex has been seen under different conditions, including glycerol gradient sedimentation and co-immunoprecipitation [23].
• As judged by proteolysis sensitivity, DnaJ is composed of three separate regions, a 9-kDa NH2-terminal domain, a 30-kDa COOH-terminal domain, and a protease-sensitive glycine- and phenylalanine-rich (G/F-rich) segment of 30 amino acids that serves as a flexible linker between the two domains [24].
• Like all J homologues, it shares homology with the highly conserved NH2-terminal "J-domain" of DnaJ [25].
• Specificity of DnaK for arginine/lysine and effect of DnaJ on the amino acid specificity of DnaK [26].

Analytical, diagnostic and therapeutic context of ECs0015

• Supporting this view, infrared and circular dichroism studies show that the DnaJ secondary structure is largely unaffected by the release of Zn(II) [27].
• Investigation of the interaction between DnaK and DnaJ by surface plasmon resonance spectroscopy [28].
• Zinc (15)N-(1)H HSQC titrations indicate that the fold of the isolated DnaJ CR domain is zinc-dependent and that one zinc module folds before the other [11].
• An enzyme-linked immunosorbent assay showed that IgG titers to the N-terminal conservative region of the DnaJ are significantly higher in RA patients compared with the healthy controls (p < 0.05) [29].
• The C. burnetii dnaJ gene was expressed in E. coli and identified by Western blot analysis using polyclonal antibodies raised against purified E. coli DnaJ protein [30].

References