Affinage

GRPEL1

GrpE protein homolog 1, mitochondrial · UniProt Q9HAV7

Round 2 corrected
Length
217 aa
Mass
24.3 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRPEL1 is a nuclear-encoded mitochondrial matrix nucleotide exchange factor (NEF) that drives the ATPase cycle of mitochondrial Hsp70 (mtHsp70) by accelerating ADP release, thereby enabling mtHsp70-dependent preprotein import, iron-sulfur cluster biogenesis, and mitochondrial protein quality control (PMID:8022808, PMID:9237899, PMID:28848044). GRPEL1 forms a homodimer in its free state and assembles into a hetero-oligomeric complex with its paralog GRPEL2, a partnership that confers mutual stability and is required for full NEF activity toward mtHsp70 (PMID:12840016, PMID:28848044). Loss of GrpEL1–mtHsp70 interaction leads to accumulation of protein aggresomes, impaired mitochondrial membrane potential, and apoptotic signaling (PMID:35093469). Dengue virus NS3 protease enters the mitochondrial matrix and cleaves GRPEL1 at KR81↓A and QR92↓S, reducing its steady-state levels during infection and in severe dengue patient samples (PMID:32581108).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1994 High

    Identification of a mitochondrial GrpE homolog answered whether eukaryotic mitochondria possess a dedicated Hsp70 nucleotide exchange factor; yeast Mge1p was shown to be an essential, nuclear-encoded, matrix-localized protein required for preprotein import.

    Evidence Yeast genetics, subcellular fractionation, import assays, co-immunoprecipitation, and ATP-dependent dissociation from mt-Hsp70 across S. cerevisiae and N. crassa

    PMID:7935381 PMID:8022808 PMID:8112465 PMID:8168496

    Open questions at the time
    • Mammalian ortholog not yet characterized
    • Mechanism of nucleotide exchange not dissected at the kinetic level
    • Structural basis of the GrpE–Hsp70 interaction unknown
  2. 1995 High

    Conditional mutant studies resolved that Mge1p promotes mt-Hsp70 cycling on translocating substrates by facilitating nucleotide-dependent substrate release, and that loss of this cycling leads to protein aggregation and incomplete folding inside mitochondria.

    Evidence Temperature-sensitive mge1 mutants with measurements of mt-Hsp70–preprotein binding, Hsp70–MIM44 dissociation, and protein aggregation in yeast mitochondria

    PMID:7628446 PMID:8524277

    Open questions at the time
    • Whether Mge1p directly contacts the translocon or acts solely through Hsp70 cycling was unresolved
    • Quantitative rate constants for ADP release not yet measured
  3. 1997 High

    Reconstitution with purified components demonstrated that Mge1p stimulates mt-Hsp70 ATPase activity by accelerating ADP release rather than phosphate release, defining its precise biochemical step in the Hsp70 catalytic cycle.

    Evidence In vitro ATPase assay with purified recombinant mt-Hsp70 and Mge1p, phosphate inhibition experiments

    PMID:9237899

    Open questions at the time
    • Whether the mechanism is conserved in mammalian GRPEL1 was not directly tested
    • Structural basis for ADP release stimulation unknown
  4. 1998 High

    Discovery that mammals encode two mitochondrial GrpE paralogs (GRPEL1 and GRPEL2), both capable of binding mt-Hsp70 and stimulating its ATPase activity, raised the question of why two NEFs are maintained.

    Evidence DnaK affinity binding, ATP dissociation assay, ATPase stimulation with purified mammalian mt-Hsp70, cDNA cloning

    PMID:9694873

    Open questions at the time
    • Functional specialization of GRPEL1 vs. GRPEL2 not addressed
    • Whether the two paralogs form a heterocomplex was unknown
  5. 2003 High

    Biophysical characterization established that free GRPEL1 forms an elongated symmetric homodimer that undergoes conformational rearrangement to an asymmetric state upon DnaK/Hsp70 binding, providing the first structural insight into the mammalian NEF.

    Evidence Analytical ultracentrifugation, SAXS, circular dichroism, and differential scanning calorimetry of human GRPEL1

    PMID:12840016

    Open questions at the time
    • High-resolution atomic structure not available
    • Whether GRPEL1 functions as a heterodimer with GRPEL2 in vivo was unknown
  6. 2017 High

    The discovery that GRPEL1 and GRPEL2 form a hetero-oligomeric complex in human cells resolved the question of paralog specialization: the heterodimer is required for mutual stability and jointly regulates mtHsp70-dependent preprotein import and Fe-S cluster biogenesis, with GRPEL2 providing stress resistance and GRPEL1 acting as a stress modulator.

    Evidence Co-immunoprecipitation, RNAi knockdown, mitochondrial import and Fe-S biogenesis assays in human cells

    PMID:28848044

    Open questions at the time
    • Stoichiometry and architecture of the heterodimer remain undefined
    • Whether heterodimer formation is regulated under stress conditions is unclear
  7. 2020 High

    Dengue virus NS3 protease was shown to target GRPEL1 for proteolytic cleavage inside the mitochondrial matrix at two defined sites, establishing GRPEL1 destruction as a viral strategy to disrupt mitochondrial protein homeostasis.

    Evidence In vitro cleavage with purified NS3 protease, cleavage-site mutagenesis, mitochondrial import of NS3, Western blotting in virus-infected cells and severe dengue clinical samples

    PMID:32581108

    Open questions at the time
    • Whether GRPEL2 is also cleaved by NS3 was not tested
    • Downstream consequences of GRPEL1 cleavage on Fe-S biogenesis and import in infected cells not measured
  8. 2022 Medium

    Functional rescue experiments in neurons after subarachnoid hemorrhage demonstrated that loss of the GRPEL1–mtHsp70 complex leads to protein aggresome accumulation, mitochondrial depolarization, and caspase-9-dependent apoptosis, directly linking GRPEL1's NEF function to mitochondrial protein quality control and cell survival.

    Evidence GrpEL1 overexpression in primary neurons, co-IP, aggresome staining, JC-1 assay, ATP measurement, cleaved caspase-9 Western blot

    PMID:35093469

    Open questions at the time
    • Findings from a single lab in one disease model; independent replication needed
    • Whether GRPEL2 compensates for GRPEL1 loss in this context was not addressed
    • Causal link between specific GRPEL1–mtHsp70 substrates and aggresome formation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the human GRPEL1–GRPEL2–mtHsp70 ternary complex, the mechanism governing heterodimer vs. homodimer assembly, and whether GRPEL1 plays roles in additional mitochondrial pathways beyond import and Fe-S cluster biogenesis.
  • No high-resolution structure of the human GRPEL1–mtHsp70 complex exists
  • Regulation of GRPEL1–GRPEL2 heterodimer assembly is unexplored
  • Complete substrate repertoire of GRPEL1-dependent mtHsp70 activity is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 8
Pathway
R-HSA-9609507 Protein localization 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 1
Partners
GRPEL2HSPA9
Complex memberships
GRPEL1–GRPEL2 hetero-oligomeric NEF complexmtHsp70–GRPEL1/GRPEL2 chaperone complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Mge1p (yeast mitochondrial GrpE/GRPEL1 ortholog) was identified as the first eukaryotic GrpE-related protein, shown to be an essential nuclear-encoded soluble protein of the mitochondrial matrix that cooperates with mitochondrial Hsp70 (mt-Hsp70) in protein translocation into mitochondria; cells with reduced Mge1p accumulate mitochondrial precursor proteins. Yeast genetics, subcellular fractionation, precursor import assay Proceedings of the National Academy of Sciences of the United States of America High 8022808
1994 Yeast GrpEp (GRPEL1 ortholog) is made as a precursor that is cleaved upon import into mitochondria, physically interacts with mitochondrial Hsp70 (mt-Hsp70) via ATP-sensitive binding, is essential for viability, and functions analogously to bacterial GrpE with DnaK. Affinity purification with His-tagged mt-Hsp70, ATP dissociation assay, gene cloning, microsequencing, mitochondrial import assay The EMBO journal High 8168496
1994 Yeast Yge1p (GRPEL1 ortholog) localizes to the mitochondrial matrix as a soluble protein, physically interacts with mitochondrial Hsp70 (Ssc1p) by co-immunoprecipitation, is essential for cell viability, and is required for protein import into mitochondria (depletion causes precursor accumulation of F1-ATPase β subunit). Co-immunoprecipitation, subcellular fractionation, in vivo precursor accumulation assay FEBS letters High 8112465 8166717
1994 Mitochondrial GrpE (MGE, GRPEL1 ortholog) in Neurospora crassa and S. cerevisiae is quantitatively bound to matrix mt-Hsp70, released by Mg-ATP (but not non-hydrolyzable analogs or high salt), and co-precipitates with preproteins in transit across mitochondrial membranes, demonstrating that mt-Hsp70 and MGE cooperate in membrane translocation. Immunoprecipitation with anti-MGE and anti-mt-Hsp70 antibodies, ATP-dependent dissociation assay, import intermediate trapping Molecular and cellular biology High 7935381
1995 Yeast Mge1p (GRPEL1 ortholog) conditional mutants impair mt-Hsp70 binding to incoming precursor proteins, reduce nucleotide-dependent dissociation of mt-Hsp70 from MIM44, and cause increased protein aggregation and incomplete folding of newly imported proteins; Mge1p promotes the progress of the Hsp70 reaction cycle for protein import and folding. Temperature-sensitive mge1 mutants, mitochondrial import kinetics assay, mt-Hsp70–MIM44 interaction assay, protein aggregation assay The EMBO journal High 7628446
1995 Yeast Mge1p (GRPEL1 ortholog) mutant mitochondria show defective mt-Hsp70 binding to translocating precursors and impaired maturation (retarded second proteolytic processing); wild-type Mge1p promotes mt-Hsp70 cycling by modulating nucleotide-dependent substrate binding. Conditional mge1 mutants, preprotein import assay, proteolytic processing assay, mt-Hsp70–preprotein interaction measurements Molecular and cellular biology High 8524277
1997 Yeast Mge1p (GRPEL1 ortholog) stimulates ATP hydrolysis by mt-Hsp70 approximately 2-fold and promotes the ATPase cycle by increasing the rate of ADP release rather than directly affecting phosphate release; inorganic phosphate inhibits ATP hydrolysis by preventing ADP release, and Mge1p relieves this phosphate inhibition. In vitro ATPase assay with purified recombinant mt-Hsp70 and Mge1p, phosphate inhibition experiments Journal of molecular biology High 9237899
1996 Rat mitochondrial GrpE (mt-GrpE, GRPEL1 ortholog) is a 21 kDa nuclear-encoded protein present exclusively in the mitochondrial fraction; its transcript is expressed in most organs; unlike other mitochondrial chaperones, mt-GrpE levels are only marginally increased by heat shock or proline analog stress, suggesting constitutive expression. cDNA cloning, Western blotting of subcellular fractions, Northern blotting across tissues, stress induction experiments FEBS letters Medium 8914984
1998 Two mammalian mitochondrial GrpE-like proteins (mt-GrpE#1/GRPEL1 and mt-GrpE#2/GRPEL2) were identified; both bind specifically to E. coli DnaK in an ATP-dissociable manner, interact with mammalian mt-Hsp70, and stimulate its ATPase activity; they share ~47% amino acid identity and differ in 3'-UTR destabilization elements, suggesting different post-transcriptional regulation. DnaK affinity binding assay, ATP dissociation, ATPase stimulation assay with purified mammalian mt-Hsp70, cDNA cloning, sequence analysis The Journal of biological chemistry High 9694873
2001 Human HMGE (GRPEL1 ortholog) was identified as a mitochondrial protein that co-purifies with E. coli DnaK and is released by Mg-ATP; it also binds cytosolic Hsc70 and the DnaJ-domain protein HSJ1b; HMGE inhibits HSJ1b-enhanced Hsc70 ATPase activity and may interact directly with DnaJ proteins, representing the first reported DnaJ–GrpE direct interaction. GST pulldown with DnaK, ATP dissociation assay, subcellular fractionation, immunocytochemistry, co-immunoprecipitation with Hsc70 and HSJ1b, ATPase inhibition assay Gene Medium 11311562
2003 Free human mitochondrial GrpE (GRPEL1) forms a symmetric dimer in solution, with an elongated cruciform shape as determined by analytical ultracentrifugation and small-angle X-ray scattering; the symmetric dimer becomes asymmetric upon DnaK binding, suggesting a conformational change upon complex formation. Circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, small-angle X-ray scattering (SAXS) The Journal of biological chemistry High 12840016
2017 Human GrpEL1 and GrpEL2 both associate with mtHsp70 as a hetero-oligomeric subcomplex in human cells; this hetero-oligomeric complex formation is critical for conferring stability to both NEFs; GrpEL1 and GrpEL2 together regulate mtHsp70-dependent import of preproteins and biogenesis of Fe-S clusters; GrpEL2 has evolved as a stress-resistance protein, while GrpEL1 functions as a stress modulator. Co-immunoprecipitation, RNAi knockdown, mitochondrial preprotein import assay, Fe-S cluster biogenesis assay, stability assays The Journal of biological chemistry High 28848044
2020 Dengue virus NS3 protease is imported into the mitochondrial matrix via an intrinsic mitochondrial transport signal and cleaves GrpEL1 at sites KR81A and QR92S; GrpEL1 levels are reduced in NS3-expressing cells, NS3-helicase-expressing cells, virus-infected cells, and severe dengue clinical samples, identifying GrpEL1 as a substrate of dengue NS3 protease. In silico MTS prediction, transient transfection, mitochondrial import assay, purified component cleavage assay, site mapping, Western blotting in clinical samples Journal of virology High 32581108
2022 After subarachnoid hemorrhage (SAH), the GrpEL1–mtHsp70 complex is reduced in neurons; overexpression of GrpEL1 increases GrpEL1–mtHsp70 complex formation (by co-immunoprecipitation), decreases protein aggresomes, improves mitochondrial membrane potential, increases ATP content, and decreases cleaved Caspase-9, demonstrating that the GrpEL1–mtHsp70 interaction is essential for mitochondrial protein quality control and neuronal survival after SAH. Co-immunoprecipitation, aggresome staining, JC-1 mitochondrial membrane potential assay, ATP measurement, Western blot (cleaved Caspase-9), GrpEL1 overexpression in primary neurons Brain research bulletin Medium 35093469
2020 GRPEL1 was identified as a physical interactor of SARS-CoV-2 proteins by affinity-purification mass spectrometry in human cells, placing it within the host-virus protein interaction network. Affinity-purification mass spectrometry (AP-MS) of tagged SARS-CoV-2 proteins in HEK293T cells Nature Low 32353859

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1991 Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proceedings of the National Academy of Sciences of the United States of America 744 1826368
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
1993 DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. The EMBO journal 531 7900997
1994 The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proceedings of the National Academy of Sciences of the United States of America 453 7937953
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
1997 Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. Science (New York, N.Y.) 410 9103205
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2011 IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nature immunology 405 21642987
1998 Chaperone coexpression plasmids: differential and synergistic roles of DnaK-DnaJ-GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar pollen, Cryj2, in Escherichia coli. Applied and environmental microbiology 346 9572938
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1997 GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1. The EMBO journal 321 9321400
2019 Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality. Cancer cell 298 31056398
1999 ClpB cooperates with DnaK, DnaJ, and GrpE in suppressing protein aggregation. A novel multi-chaperone system from Escherichia coli. The Journal of biological chemistry 290 10497158
1992 Physical interaction between heat shock proteins DnaK, DnaJ, and GrpE and the bacterial heat shock transcription factor sigma 32. Cell 282 1534276
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
1989 Initiation of lambda DNA replication with purified host- and bacteriophage-encoded proteins: the role of the dnaK, dnaJ and grpE heat shock proteins. The EMBO journal 272 2527744
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
1996 A cycle of binding and release of the DnaK, DnaJ and GrpE chaperones regulates activity of the Escherichia coli heat shock transcription factor sigma32. The EMBO journal 232 8599944
1999 Heat-inactivated proteins are rescued by the DnaK.J-GrpE set and ClpB chaperones. Proceedings of the National Academy of Sciences of the United States of America 211 10377389
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
1997 GrpE accelerates nucleotide exchange of the molecular chaperone DnaK with an associative displacement mechanism. Biochemistry 155 9131990
1995 The DnaK chaperone system of Escherichia coli: quaternary structures and interactions of the DnaK and GrpE components. The Journal of biological chemistry 154 7836448
2010 A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal 153 20186120
1987 The grpE protein of Escherichia coli. Purification and properties. The Journal of biological chemistry 152 2826421
1994 A role for a eukaryotic GrpE-related protein, Mge1p, in protein translocation. Proceedings of the National Academy of Sciences of the United States of America 150 8022808
1994 A mitochondrial homolog of bacterial GrpE interacts with mitochondrial hsp70 and is essential for viability. The EMBO journal 149 8168496
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
1992 DnaK, DnaJ, and GrpE are required for flagellum synthesis in Escherichia coli. Journal of bacteriology 141 1400176
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2022 Human transcription factor protein interaction networks. Nature communications 123 35140242
1995 Modulation of the ATPase activity of the molecular chaperone DnaK by peptides and the DnaJ and GrpE heat shock proteins. The Journal of biological chemistry 123 7876226
1994 A conserved loop in the ATPase domain of the DnaK chaperone is essential for stable binding of GrpE. Nature structural biology 118 7656024
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2021 Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 113 34349018
2015 KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II. Molecular cell 113 26725010
1993 Both the Escherichia coli chaperone systems, GroEL/GroES and DnaK/DnaJ/GrpE, can reactivate heat-treated RNA polymerase. Different mechanisms for the same activity. The Journal of biological chemistry 111 7902351
1996 Identification of a Caulobacter crescentus operon encoding hrcA, involved in negatively regulating heat-inducible transcription, and the chaperone gene grpE. Journal of bacteriology 110 8606155
1992 Molecular characterization of the dnaK gene region of Clostridium acetobutylicum, including grpE, dnaJ, and a new heat shock gene. Journal of bacteriology 110 1577695
1997 The power stroke of the DnaK/DnaJ/GrpE molecular chaperone system. Journal of molecular biology 109 9223639
2021 Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity. Nature communications 107 34599178
1997 Transcriptional analysis of the Streptococcus mutans hrcA, grpE and dnaK genes and regulation of expression in response to heat shock and environmental acidification. Molecular microbiology 99 9282745
2001 The chloroplastic GrpE homolog of Chlamydomonas: two isoforms generated by differential splicing. The Plant cell 97 11752390
1989 The heat-shock-regulated grpE gene of Escherichia coli is required for bacterial growth at all temperatures but is dispensable in certain mutant backgrounds. Journal of bacteriology 97 2651417
2003 GrpE, a nucleotide exchange factor for DnaK. Cell stress & chaperones 93 14984054
1996 Involvement of the DnaK-DnaJ-GrpE chaperone team in protein secretion in Escherichia coli. Journal of bacteriology 88 8655561
1990 Roles of Escherichia coli heat shock proteins DnaK, DnaJ and GrpE in mini-F plasmid replication. Molecular & general genetics : MGG 88 2183004
1995 The role of the GrpE homologue, Mge1p, in mediating protein import and protein folding in mitochondria. The EMBO journal 82 7628446
1986 Escherichia coli grpE gene codes for heat shock protein B25.3, essential for both lambda DNA replication at all temperatures and host growth at high temperature. Journal of bacteriology 82 2424889
1994 Mitochondrial GrpE is present in a complex with hsp70 and preproteins in transit across membranes. Molecular and cellular biology 78 7935381
1992 DnaJ, DnaK, and GrpE heat shock proteins are required in oriP1 DNA replication solely at the RepA monomerization step. Proceedings of the National Academy of Sciences of the United States of America 76 1438220
1994 YGE1 is a yeast homologue of Escherichia coli grpE and is required for maintenance of mitochondrial functions. FEBS letters 75 8112465
1998 The Hsc66-Hsc20 chaperone system in Escherichia coli: chaperone activity and interactions with the DnaK-DnaJ-grpE system. Journal of bacteriology 74 9852006
1989 Participation of Escherichia coli heat shock proteins DnaJ, DnaK, and GrpE in P1 plasmid replication. Journal of bacteriology 74 2681150
1998 Control of the DnaK chaperone cycle by substoichiometric concentrations of the co-chaperones DnaJ and GrpE. The Journal of biological chemistry 70 9506960
1993 Initiation of lambda DNA replication. The Escherichia coli small heat shock proteins, DnaJ and GrpE, increase DnaK's affinity for the lambda P protein. The Journal of biological chemistry 70 8444859
1992 Activity of the Hsp70 chaperone complex--DnaK, DnaJ, and GrpE--in initiating phage lambda DNA replication by sequestering and releasing lambda P protein. Proceedings of the National Academy of Sciences of the United States of America 66 1361234
1995 Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and maturation of preproteins. Molecular and cellular biology 64 8524277
1998 Temperature-controlled activity of DnaK-DnaJ-GrpE chaperones: protein-folding arrest and recovery during and after heat shock depends on the substrate protein and the GrpE concentration. Biochemistry 63 9657681
2004 Influence of GrpE on DnaK-substrate interactions. The Journal of biological chemistry 60 15102842
2011 Recent gene duplication and subfunctionalization produced a mitochondrial GrpE, the nucleotide exchange factor of the Hsp70 complex, specialized in thermotolerance to chronic heat stress in Arabidopsis. Plant physiology 59 22128139
2001 Folding properties of the nucleotide exchange factor GrpE from Thermus thermophilus: GrpE is a thermosensor that mediates heat shock response. Journal of molecular biology 59 11724541
1988 Sequence analysis and transcriptional regulation of the Escherichia coli grpE gene, encoding a heat shock protein. Nucleic acids research 59 3045760
1989 Escherichia coli DnaK and GrpE heat shock proteins interact both in vivo and in vitro. Journal of bacteriology 58 2522091
2005 The heat shock genes dnaK, dnaJ, and grpE are involved in regulation of putisolvin biosynthesis in Pseudomonas putida PCL1445. Journal of bacteriology 57 16109938
1993 Isolation of dnaJ, dnaK, and grpE homologues from Borrelia burgdorferi and complementation of Escherichia coli mutants. Molecular microbiology 53 8459764
1993 Heat shock proteins DnaJ, DnaK, and GrpE stimulate P1 plasmid replication by promoting initiator binding to the origin. Journal of bacteriology 53 8501058
2014 Interplay between E. coli DnaK, ClpB and GrpE during protein disaggregation. Journal of molecular biology 51 25451597
2015 GrpE, Hsp110/Grp170, HspBP1/Sil1 and BAG domain proteins: nucleotide exchange factors for Hsp70 molecular chaperones. Sub-cellular biochemistry 48 25487014
2017 Regulation of mitochondrial protein import by the nucleotide exchange factors GrpEL1 and GrpEL2 in human cells. The Journal of biological chemistry 47 28848044
2004 Escherichia coli Hsp31 functions as a holding chaperone that cooperates with the DnaK-DnaJ-GrpE system in the management of protein misfolding under severe stress conditions. Molecular microbiology 47 14731284
2012 Crystal structure of DnaK protein complexed with nucleotide exchange factor GrpE in DnaK chaperone system: insight into intermolecular communication. The Journal of biological chemistry 45 22544739
1994 Yge1p, a eukaryotic Grp-E homolog, is localized in the mitochondrial matrix and interacts with mitochondrial Hsp70. Biochemical and biophysical research communications 45 8166717
1979 Subnucleosome particles containing high mobility group proteins HMG-E and HMG-G originate from transcriptionally active chromatin. Nucleic acids research 44 503859
1998 Evidence for the existence of distinct mammalian cytosolic, microsomal, and two mitochondrial GrpE-like proteins, the Co-chaperones of specific Hsp70 members. The Journal of biological chemistry 43 9694873
1997 Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70. Journal of molecular biology 43 9237899
1996 Protein folding in the cytoplasm of Escherichia coli: requirements for the DnaK-DnaJ-GrpE and GroEL-GroES molecular chaperone machines. Molecular microbiology 43 8898387
2008 The proper ratio of GrpE to DnaK is important for protein quality control by the DnaK-DnaJ-GrpE chaperone system and for cell division. Microbiology (Reading, England) 42 18599817
2005 Dimeric trigger factor stably binds folding-competent intermediates and cooperates with the DnaK-DnaJ-GrpE chaperone system to allow refolding. The Journal of biological chemistry 38 15632130
2001 Mutations in the interdomain linker region of DnaK abolish the chaperone action of the DnaK/DnaJ/GrpE system. FEBS letters 38 11376662
2006 Tuning of DnaK chaperone action by nonnative protein sensor DnaJ and thermosensor GrpE. The Journal of biological chemistry 37 16940296
1996 Structure-function analysis of the Escherichia coli GrpE heat shock protein. The EMBO journal 37 8890154
1994 Identification of a grpE heat-shock gene homolog in the archaeon Methanosarcina mazei. Journal of molecular biology 35 7517454
1994 Isolation and characterization of point mutations in the Escherichia coli grpE heat shock gene. Journal of bacteriology 35 7961459
1993 The interplay of the GrpE heat shock protein and Mg2+ in RepA monomerization by DnaJ and DnaK. The Journal of biological chemistry 34 8244960
1978 A transducing lambda phage carrying grpE, a bacterial gene necessary for lambda DNA replication, and two ribosomal protein genes, rpsP (S16) and rplS (L19). Molecular & general genetics : MGG 34 368561
2018 Mycobacterium tuberculosis GrpE, A Heat-Shock Stress Responsive Chaperone, Promotes Th1-Biased T Cell Immune Response via TLR4-Mediated Activation of Dendritic Cells. Frontiers in cellular and infection microbiology 32 29637049
1996 Isolation and characterisation of a cDNA encoding rat mitochondrial GrpE, a stress-inducible nucleotide-exchange factor of ubiquitous appearance in mammalian organs. FEBS letters 30 8914984
2003 Free human mitochondrial GrpE is a symmetric dimer in solution. The Journal of biological chemistry 27 12840016
2001 A GrpE mutant containing the NH(2)-terminal "tail" region is able to displace bound polypeptide substrate from DnaK. Biochemical and biophysical research communications 25 11401497
2000 Phylogenetic analysis of gram-positive bacteria based on grpE, encoded by the dnaK operon. International journal of systematic and evolutionary microbiology 25 11034484
1997 Chloroplastic isoforms of DnaJ and GrpE in pea. Plant molecular biology 25 9037170
2015 Modulation of the chaperone DnaK allosterism by the nucleotide exchange factor GrpE. The Journal of biological chemistry 24 25739641
2012 Group A streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein. The Journal of biological chemistry 24 22566698
2002 Hsc62, Hsc56, and GrpE, the third Hsp70 chaperone system of Escherichia coli. Biochemical and biophysical research communications 24 12054669
2003 Induced expression of the heat shock protein genes uspA and grpE during starvation at low temperatures and their influence on thermal resistance of Escherichia coli O157:H7. Journal of food protection 23 14627281
1997 K+ is an indispensable cofactor for GrpE stimulation of ATPase activity of DnaK x DnaJ complex from Thermus thermophilus. FEBS letters 23 9276481
2020 Mitochondrial Import of Dengue Virus NS3 Protease and Cleavage of GrpEL1, a Cochaperone of Mitochondrial Hsp70. Journal of virology 22 32581108
2005 Effects of environmental stresses on the activities of the uspA, grpE and rpoS promoters of Escherichia coli O157:H7. International journal of food microbiology 22 15718032
2022 GrpEL1 regulates mitochondrial unfolded protein response after experimental subarachnoid hemorrhage in vivo and in vitro. Brain research bulletin 21 35093469
2009 Crystal structure of a thermophilic GrpE protein: insight into thermosensing function for the DnaK chaperone system. Journal of molecular biology 21 20036249
1993 Activation of mutant forms of DnaA protein of Escherichia coli by DnaK and GrpE proteins occurs prior to DNA replication. The Journal of biological chemistry 21 8514753
2007 GrpE N-terminal domain contributes to the interaction with Dnak and modulates the dynamics of the chaperone substrate binding domain. Journal of molecular biology 20 17976642
2024 Structure of the M. tuberculosis DnaK-GrpE complex reveals how key DnaK roles are controlled. Nature communications 19 38253530
2004 The DnaK-DnaJ-GrpE chaperone system activates inert wild type pi initiator protein of R6K into a form active in replication initiation. The Journal of biological chemistry 19 15485812
2009 Cloning and characterization of grpE in Acetobacter pasteurianus NBRC 3283. Journal of bioscience and bioengineering 18 20129077
2005 The heat-sensitive Escherichia coli grpE280 phenotype: impaired interaction of GrpE(G122D) with DnaK. Journal of molecular biology 18 16198374
2001 The effect of co-overproduction of DnaK/DnaJ/GrpE and ClpB proteins on the removal of heat-aggregated proteins from Escherichia coli DeltaclpB mutant cells--new insight into the role of Hsp70 in a functional cooperation with Hsp100. FEMS microbiology letters 18 11731148
1993 Activation of DnaA5 protein by GrpE and DnaK heat shock proteins in initiation of DNA replication in Escherichia coli. The Journal of biological chemistry 18 8390456
2007 A gram-negative characteristic segment in Escherichia coli DnaK is essential for the ATP-dependent cooperative function with the co-chaperones DnaJ and GrpE. FEBS letters 17 17544398
2001 Identification and characterization of a human mitochondrial homologue of the bacterial co-chaperone GrpE. Gene 17 11311562
2000 Heat-inactivated proteins managed by DnaKJ-GrpE-ClpB chaperones are released as a chaperonin-recognizable non-native form. The Journal of biological chemistry 17 10777521
1995 Archaeal grpE: transcription in two different morphologic stages of Methanosarcina mazei and comparison with dnaK and dnaJ. Journal of bacteriology 17 7836285
2020 GrpE Immunization Protects Against Ureaplasma urealyticum Infection in BALB/C Mice. Frontiers in immunology 16 32849509
2018 Comparison of immunogenicity and vaccine efficacy between heat-shock proteins, HSP70 and GrpE, in the DnaK operon of Mycobacterium tuberculosis. Scientific reports 16 30258084
2001 Characterization of stress-responsive genes, hrcA-grpE-dnaK-dnaJ, from phytopathogenic Xanthomonas campestris. Archives of microbiology 16 11479711
2006 Low resolution structure and stability studies of human GrpE#2, a mitochondrial nucleotide exchange factor. Archives of biochemistry and biophysics 15 16579957
1992 The essential Escherichia coli msgB gene, a multicopy suppressor of a temperature-sensitive allele of the heat shock gene grpE, is identical to dapE. Journal of bacteriology 15 1644751