Disease relevance of grpE

• The crystal structure of the adenine nucleotide exchange factor GrpE in complex with the adenosine triphosphatase (ATPase) domain of Escherichia coli DnaK [heat shock protein 70 (Hsp70)] was determined at 2.8 angstrom resolution [1].
• The DnaK, DnaJ, and GrpE proteins have been known to function in various biological situations, including bacteriophage lambda replication [2].
• Here, we analysed the thermal stability of GrpE from Thermus thermophilus using differential scanning calorimetry and CD-spectroscopy [3].
• Functional characterisation of the chaperones DnaK, DnaJ, and GrpE from Clostridium acetobutylicum [4].

High impact information on grpE

• Dependent on GrpE and ATP hydrolysis, the protein is then transferred to GroEL (heat-shock protein 60) which acts catalytically in the production of the native state [5].
• We report that two other heat shock proteins, DnaJ and GrpE, are also involved in the negative regulation of heat shock gene expression [6].
• Our results also demonstrate that both the N-terminal and C-terminal regions are important for GrpE function in lambda DNA replication and its co-chaperone activity with DnaK [7].
• The chaperone system formed by DnaK, DnaJ and GrpE mediates stress-dependent negative modulation of the Escherichia coli heat shock response, probably through association with the heat shock promoter-specific sigma32 subunit of RNA polymerase [8].
• All of them, GrpE103, GrpE66, GrpE2/280, GrpE17, GrpE13a and GrpE25, have single amino acid substitutions located in highly conserved regions throughout the GrpE sequence [7].

Chemical compound and disease context of grpE

• When the E. coli chaperone genes GroEL, GroES, DnaK, DnaJ and GrpE were coexpressed with manganese catalase, a significant fraction of the overproduced protein was partitioned into the soluble fraction [9].

Biological context of grpE

• The second system includes the E.coli grpE protein and is termed 'grpE-dependent'. Both systems are specific for plasmid molecules carrying the ori lambda DNA initiation site [10].
• At least three heat shock proteins, DnaK, DnaJ and GrpE, are involved in negative modulation of the sigma 32-dependent heat shock response [11].
• Three of the heat shock proteins, DnaK, DnaI, and GrpE, play a central role in the negative autoregulation of this response at the transcriptional level [12].
• The co-chaperone GrpE is essential for the activities of the Hsp70 system, which assists protein folding [13].
• Real time kinetics of the DnaK/DnaJ/GrpE molecular chaperone machine action [14].

Anatomical context of grpE

• GrpE caused dissociation of the peptide from the ribosome; ATP was required for this reaction [15].
• Its three members, DnaK, DnaJ, and GrpE, in Escherichia coli work synergistically to promote protein protection, disaggregation, and import into the various organelles [16].
• These results suggest that GrpE may have a previously unsuspected function(s) in cell wall biosynthesis in E. coli [17].

Associations of grpE with chemical compounds

• We conclude that in the presence of DnaJ and GrpE, the binding-release cycle of DnaK is stoichiometrically coupled to the adenosine triphosphatase activity of DnaK [14].
• Components necessary during the first stage for "activation" included GrpE and DnaK proteins, ATP at 0.2 mM or greater, and polyvinyl alcohol (8%) or glycerol, optimal at concentrations between 20 and 30% [18].
• EDTA or physiological metabolites, including citrate, phosphate, pyrophosphate, and ATP, all elicit the GrpE requirement [19].
• DnaK756 has three glycine-to-aspartate substitutions at residues 32, 455, and 468, which were reported to result in defects in intrinsic and GrpE-stimulated ATPase activities, substrate binding, stability of the substrate-binding domain, interdomain communication, and, consequently, defects in chaperone activity [20].
• The activation of the cps operon by DjIA is dependent upon both DnaK(Hsp70) and GrpE, and therefore we propose a role for DjIA, together with this chaperone machine, as a novel regulator of a two-component histidine kinase signal transduction pathway [21].

Other interactions of grpE

• It acts as a multicopy suppressor for dnaJ mutations and functions in vitro in combination with DnaK and GrpE in protein remodeling reactions [22].

Analytical, diagnostic and therapeutic context of grpE

• The behavior of DnaK and GrpE in gel filtration and dynamic light scattering suggested elongated shapes of both molecules [23].
• Thermal unfolding of human GrpE measured both by circular dichroism and differential scanning calorimetry differs from that of prokaryotic GrpE [13].
• Using immunoprecipitation, we show that in the presence of GrpE, DnaK exhibits a higher affinity for the lambda P.DnaJ complex than it does alone [24].
• Based on recent replication work indicating an important role for the GrpE heat shock protein, we have used electron microscopy to study the action of GrpE in the DNA unwinding and replication reactions [25].
• We find that Mdj1pDelta55 interacts with DnaK as judged both by an enzyme-linked immunosorbent assay, as well as stimulation of DnaK's weak ATPase activity in the presence of GrpE [26].

References