Affinage

HSPE1

10 kDa heat shock protein, mitochondrial · UniProt P61604

Round 2 corrected
Length
102 aa
Mass
10.9 kDa
Annotated
2026-04-28
130 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPE1 encodes the mitochondrial co-chaperonin HSP10, a heptameric ring that caps one end of the HSP60 (HSPD1) double-toroid chaperonin in an ATP-driven asymmetric cycle, converting the folding cavity from a hydrophobic substrate-binding state to an enlarged hydrophilic enclosure that permits enclosed protein folding and release (PMID:9285585, PMID:7901770). The HSP60–HSP10 complex is the most abundant mitochondrial chaperonin, engaging approximately half of all annotated matrix proteins—including respiratory chain subunits and SOD2—and its assembly is regulated by SIRT4-mediated deacetylation of HSP60 (PMID:32060690, PMID:38329114). Beyond canonical folding, HSP10 recruits mitochondrial Hsp70 to promote biogenesis of Hsp60 oligomers, participates in pro-caspase-3 activation with HSP60 upon mitochondrial release, and protects against oxidative protein damage in skeletal muscle (PMID:25792736, PMID:10205158, PMID:20410481). A de novo heterozygous HSPE1 missense mutation (p.Leu73Phe) destabilizes the protein, reduces SOD2 levels, elevates mitochondrial superoxide, and causes infantile spasms, establishing HSPE1 as a neurological disease gene (PMID:27774450).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1986 High

    Establishing that the co-chaperonin (GroES/HSP10 ortholog) physically associates with the chaperonin (GroEL/HSP60) in an ATP- and Mg²⁺-dependent manner and inhibits its ATPase activity resolved the fundamental question of whether these two heat-shock proteins form a functional unit.

    Evidence Gel filtration, co-sedimentation, affinity chromatography, and ATPase assay on purified bacterial GroES and GroEL

    PMID:3017973

    Open questions at the time
    • Stoichiometry of the complex not yet defined
    • Whether interaction occurs in mitochondria unknown
    • No structural data on the complex
  2. 1990 High

    Demonstrating that mitochondria contain a functional HSP10 homolog that can replace bacterial GroES in chaperonin-dependent protein refolding established the mitochondrial co-chaperonin system as a conserved folding machine.

    Evidence In vitro RuBisCO refolding reconstitution with purified mitochondrial cpn10 substituting for bacterial cpn10

    PMID:1977163

    Open questions at the time
    • Identity of endogenous mitochondrial substrates unknown
    • No gene cloning or sequence data for mammalian HSPE1 at this point
  3. 1992 High

    Electron microscopy and biochemical analyses established that GroES binds asymmetrically to one ring of the GroEL 14-mer (1:1 stoichiometry), triggering conformational changes in both rings and accommodating substrate within the central cavity, resolving the architecture of the active folding complex.

    Evidence Electron microscopy, proteolytic protection, ATPase assay on GroEL–GroES complexes

    PMID:1352285 PMID:1361169

    Open questions at the time
    • Atomic-resolution structure not yet available
    • Whether encapsulation or trans-ring release mediates folding is unresolved
  4. 1994 High

    Genetic studies in yeast proved that mitochondrial Hsp10 is essential for viability, required for folding of matrix-imported proteins and for sorting of proteins transiting through the matrix, and that temperature-sensitive mutations map to the mobile loop region critical for Hsp60 binding.

    Evidence Temperature-sensitive hsp10 mutants in yeast, in vivo import and folding assays, binding affinity measurements

    PMID:7913473 PMID:7916344

    Open questions at the time
    • Mammalian in vivo essentiality not yet demonstrated
    • Full substrate repertoire of Hsp10 unknown
    • Degree of Hsp10-independent Hsp60 activity in vivo unclear
  5. 1997 High

    The crystal structure of the GroEL–GroES–(ADP)₇ complex revealed that GroES binding doubles the central cavity volume, buries hydrophobic peptide-binding sites, and converts the cavity lining from hydrophobic to hydrophilic, providing the atomic basis for how the co-chaperonin creates a permissive folding environment.

    Evidence X-ray crystallography of the asymmetric GroEL–GroES–(ADP)₇ complex

    PMID:9285585

    Open questions at the time
    • Structure of the human HSP60–HSP10 complex not solved
    • How substrates larger than the cavity are handled is unresolved
  6. 1998 High

    Systematic identification of in vivo substrates in yeast mitochondria revealed that Hsp60 and Hsp10 do not always act as a single unit—some substrates require both, while others need only Hsp60—and that Hsp10 is critical for the assembly of Hsp60 itself, establishing a hierarchical dependency.

    Evidence In vivo folding screen with temperature-sensitive hsp60 and hsp10 yeast mutants

    PMID:9774331

    Open questions at the time
    • Full mammalian substrate repertoire not defined
    • Mechanism of Hsp10-independent Hsp60 activity not explained
  7. 1999 High

    Discovery that HSP10 and HSP60 form a mitochondrial complex with pro-caspase-3 and accelerate its activation upon release from mitochondria established an unexpected role for the co-chaperonin in apoptosis signaling beyond protein folding.

    Evidence Co-immunoprecipitation from Jurkat T cell mitochondrial fractions plus in vitro caspase-3 activation reconstitution

    PMID:10205158

    Open questions at the time
    • Whether HSP10 is required independently of HSP60 for caspase activation unclear
    • Physiological relevance in non-immune cells not established
  8. 2002 High

    Characterization of the HSPD1–HSPE1 bidirectional promoter on chromosome 2q33.1 explained the coordinated transcriptional regulation of HSP60 and HSP10, with heat shock increasing activity ~12-fold, resolving how the stoichiometric balance of the two subunits is maintained.

    Evidence Genomic sequencing, luciferase reporter assays with the bidirectional promoter

    PMID:12483302

    Open questions at the time
    • Post-transcriptional regulation of HSP10 levels not addressed
    • Whether STAT3-dependent regulation generalizes beyond ischemia not tested
  9. 2010 Medium

    Transgenic overexpression of HSP10 in mouse skeletal muscle prevented age-related loss of force generation and protein carbonyl accumulation, providing direct in vivo evidence that HSP10 is protective against oxidative damage associated with aging.

    Evidence HSP10 transgenic mouse, in situ force measurement, protein carbonyl quantification

    PMID:20410481

    Open questions at the time
    • Whether protection is HSP10-autonomous or requires HSP60 upregulation not dissected
    • Mechanism linking HSP10 to reduced carbonyls not defined
  10. 2015 High

    Identification of a direct HSP10–mtHsp70 interaction independent of HSP60 revealed that HSP10 recruits mtHsp70 to promote assembly of Hsp60 precursors into functional heptameric rings, expanding the role of HSP10 beyond co-chaperonin lid to active participant in chaperonin biogenesis.

    Evidence Co-immunoprecipitation/mass spectrometry, SILAC quantitative proteomics, in vitro assembly assay in human mitochondria

    PMID:25792736

    Open questions at the time
    • Structural basis of HSP10–mtHsp70 interaction unknown
    • Whether this pathway is regulated is not addressed
  11. 2016 High

    A de novo HSPE1 missense mutation (p.Leu73Phe) causing infantile spasms was shown to destabilize HSP10, halving the HSP10:HSP60 ratio and reducing the HSP60/HSP10 client SOD2 to ~20%, with doubled mitochondrial superoxide—establishing HSPE1 as a Mendelian neurological disease gene and linking chaperonin insufficiency to oxidative stress.

    Evidence Exome sequencing, recombinant protein stability assays, quantitative MS on patient fibroblasts, superoxide measurement

    PMID:27774450

    Open questions at the time
    • Only one family reported; additional allelic series needed
    • Whether haploinsufficiency is the sole mechanism not established
    • No animal model of this specific mutation
  12. 2020 High

    A comprehensive interactome of the HSP60/HSP10 complex identified 323 interacting proteins covering ~50% of annotated matrix proteins, with 19 abundant clients occupying >60% of chaperonin capacity, quantifying the centrality of the complex in mitochondrial proteostasis.

    Evidence SILAC metabolic labeling, cross-linking, HSP60 immunoprecipitation, and mass spectrometry in HEK293 cells

    PMID:32060690

    Open questions at the time
    • Client specificity determinants not identified
    • Whether client engagement changes under stress not tested
  13. 2024 Medium

    SIRT4-mediated deacetylation of HSP60 was shown to facilitate HSP60–HSP10 complex assembly, maintaining electron transport chain complex II/III activity and reducing ROS, revealing a nutrient-responsive (glutamine-dependent) regulatory axis controlling chaperonin function.

    Evidence In vivo burn sepsis mouse model with glutamine supplementation, SIRT4 overexpression/knockdown, acetylation and ETC activity assays

    PMID:38329114

    Open questions at the time
    • Whether SIRT4 directly modifies HSP10 is not tested
    • Generalizability beyond burn sepsis model unclear
    • Acetylation site on HSP60 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of the human HSP60–HSP10 complex, the determinants of substrate selectivity among the hundreds of mitochondrial clients, whether symmetric (football-shaped) HSP60–(HSP10)₂ complexes are functionally relevant in mammalian mitochondria, and how HSP10's apoptotic role in the cytoplasm is regulated relative to its folding role in the matrix.
  • No high-resolution structure of mammalian HSP60–HSP10 complex
  • Substrate triage rules undefined
  • Cytoplasmic versus mitochondrial function of HSP10 not mechanistically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 10 GO:0098772 molecular function regulator activity 4
Localization
GO:0005739 mitochondrion 9
Pathway
R-HSA-392499 Metabolism of proteins 11 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-5357801 Programmed Cell Death 2
Partners
BAXBCL2L1CASP3HSPA9HSPD1SIRT4
Complex memberships
HSP10-mtHsp70 complexHSP60-HSP10 chaperonin

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 GroES (the bacterial ortholog of HSPE1) forms a homo-oligomeric ring structure (~80 kDa from ~15 kDa subunits), physically interacts with GroEL in vitro in the presence of ATP and Mg2+, inhibits GroEL's ATPase activity at a 1:1 molar ratio, and binds specifically to a GroEL-affinity column, establishing a direct physical and functional interaction between the two chaperonin components. Gel filtration, glycerol gradient co-sedimentation, GroEL affinity chromatography, ATPase assay, electron microscopy The Journal of biological chemistry High 3017973
1989 Both groES and groEL gene products are essential for bacterial growth at all temperatures (17–42°C), demonstrating a fundamental role for this co-chaperonin in cell physiology beyond heat-stress response. Bacteriophage P1 transduction, genetic complementation with heterodiploid strains, polar insertion mutations Journal of bacteriology High 2563997
1989 Temperature-sensitive mutations in groES cause defective export of beta-lactamase in vivo, indicating that the GroES co-chaperonin has a chaperone function that facilitates protein export of a specific class of secreted proteins. In vivo protein export assay, temperature-sensitive groES mutants, pulse-chase analysis The EMBO journal Medium 2573517
1990 Mitochondria contain a functional homolog of bacterial chaperonin 10 (GroES/HSPE1 ortholog) that replaces bacterial cpn10 in chaperonin-dependent reconstitution of denatured RuBisCO, forms a stable complex with bacterial cpn60 in the presence of Mg·ATP, competes with bacterial cpn10 for a common saturable site on cpn60, and abolishes the uncoupled ATPase activity of cpn60 upon complex formation. In vitro RuBisCO refolding reconstitution, stable complex formation assay, competition assay, ATPase activity measurement Proceedings of the National Academy of Sciences of the United States of America High 1977163
1992 GroES binds asymmetrically to one end of the GroEL cylinder (1:1 stoichiometry of GroEL 14-mer to GroES 7-mer), triggers conformational changes in both the GroES-adjacent and opposite ends of GroEL, and the substrate protein is accommodated within the central cavity of GroEL; binding of a second GroES oligomer is prevented. Proteolytic protection assay, electron microscopy image analysis, ATPase inhibition assay The EMBO journal High 1361169
1992 GroEL and GroES cooperate with DnaK and DnaJ to prevent aggregation of newly synthesized proteins; overproduction of either GroEL/GroES or DnaK/DnaJ alone prevents aggregation in rpoH mutants, but together they are effective at physiological concentrations, demonstrating complementary functions in protein folding. In vivo aggregation assay in rpoH mutants, overexpression of chaperone pairs Proceedings of the National Academy of Sciences of the United States of America Medium 1359538
1992 GroEL and GroES together promote folding and assembly of heterotetrameric mammalian mitochondrial branched-chain alpha-keto acid decarboxylase (E1, alpha2beta2) in E. coli, with >500-fold increase in specific activity when both chaperonins are overexpressed, demonstrating that GroES is required for productive folding of a heteromeric mitochondrial substrate. Co-expression in groES/groEL mutant E. coli, enzyme activity assay, SDS-PAGE, affinity chromatography purification, gel filtration The Journal of biological chemistry High 1352285
1993 In the GroEL/GroES chaperonin reaction cycle, GroES and substrate protein counteract each other's effects on GroEL: GroES stabilizes GroEL in the ADP-bound state, while unfolded polypeptide triggers ADP and GroES release. Upon ADP-ATP exchange, GroES reassociates and ATP hydrolysis discharges the bound protein for folding, perpetuating cycles until folding is complete. In vitro reconstitution of folding cycle, nucleotide-binding analysis, kinetic dissection of reaction steps Nature High 7901770
1993 GroES is essential for reactivation of heat-inactivated RNA polymerase by GroEL; while GroES is not required for protection, it is needed for the release step of the chaperonin cycle. The groEL673 mutant cannot reactivate RNAP, and GroES reduces the amount of GroEL required for protection. In vitro RNA polymerase protection and reactivation assay, mutant chaperonin analysis The Journal of biological chemistry Medium 7902351
1994 Yeast mitochondrial Hsp10 (the HSPE1 ortholog) is an essential component of the mitochondrial protein folding apparatus: it is required for folding and assembly of matrix-imported proteins and for sorting of certain proteins (e.g., Rieske Fe/S protein) passing through the matrix en route to the intermembrane space. Temperature-sensitive mutations in Hsp10 map to residues 25–40 (the mobile loop region) and reduce binding affinity for Hsp60 at non-permissive temperature. Yeast genetics, temperature-sensitive lethal hsp10 mutants, in vivo import and folding assays, binding affinity measurements The Journal of cell biology High 7913473
1994 GroEL/GroES-associated degradation of an abnormal protein (CRAG) requires GroES: in a temperature-sensitive groES mutant, CRAG is completely stable at the non-permissive temperature and accumulates bound to GroEL, indicating that GroES action subsequent to GroEL binding is required for facilitating degradation of proteins that cannot be productively folded. In vivo pulse-chase degradation assay, temperature-sensitive groES mutant analysis, co-immunoprecipitation of chaperonin-substrate complex The Journal of biological chemistry Medium 7916344
1994 Cryo-EM visualization shows GroES binds to the opposite end of GroEL from the bound substrate protein (malate dehydrogenase), and ATP/GroES binding causes a dramatic ~60° hinge opening of the GroEL apical domains, establishing the structural basis for GroES-driven conformational change. Cryo-electron microscopy Nature High 7915827
1995 The GroEL-GroES interaction follows an asymmetric, ATP-driven cycle: GroES association and ATP hydrolysis in the interacting GroEL toroid form a stable GroEL:ADP:GroES complex; this complex dissociates upon ATP hydrolysis in the opposite ring without formation of a symmetric GroEL:(GroES)2 intermediate; dissociation is accelerated by unfolded polypeptide, demonstrating substrate protein plays an active role in modulating the chaperonin reaction cycle. Surface plasmon resonance kinetics (BIAcore), quantitative binding analysis Science High 7638601
1995 GroES heptamers exist in a concentration-dependent monomer-heptamer equilibrium with a dissociation constant of ~1×10⁻³⁸ M⁶ for native GroES, exhibiting dynamic subunit exchange within minutes, a feature that may be important for GroES function in the folding cycle. Fluorescence spectroscopy, light scattering, sedimentation equilibrium, native PAGE subunit exchange experiments Biochemistry Medium 7654686
1996 GroEL-bound substrate polypeptide can induce GroES cycling on and off GroEL in the presence of ADP alone (without ATP hydrolysis), promoting efficient folding of rhodanese. This establishes that neither ATP hydrolysis energy nor inter-ring allostery is strictly required for GroEL/GroES-mediated protein folding; the minimal mechanism is binding and release of GroES closing and opening the GroEL folding cage. In vitro rhodanese folding assay with ADP substitution, single-ring GroEL variant, kinetic analysis The EMBO journal High 8947033
1997 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 complex reveals that GroES binding triggers large en bloc movements of the cis ring's intermediate and apical domains, doubling the volume of the central cavity, burying hydrophobic peptide-binding residues at the GroEL-GroES interface, and converting the cavity lining from hydrophobic to hydrophilic. An inward tilt of the cis equatorial domain causes an outward tilt in the trans ring that provides negative allosteric opposition to a second GroES binding. X-ray crystallography (crystal structure of GroEL-GroES-(ADP)7 complex) Nature High 9285585
1997 GroES promotes the T-to-R allosteric transition of the GroEL ring distal to GroES in the GroEL-GroES complex, with the allosteric constant L2' for this transition (~4×10⁻⁵) being much higher than L2 for the second ring of free GroEL (~2×10⁻⁹), facilitating release of substrate proteins from trans ternary complexes. Kinetic analysis of ATP hydrolysis rates, allosteric modeling, Hill equation fitting, partition function analysis Biochemistry Medium 9315866
1997 The affinity between GroES and GroEL is regulated by temperature: as temperature increases, GroES affinity for GroEL decreases and protein release from the chaperonin concomitantly decreases; after heat shock, GroES rebinding to GroEL correlates with restoration of optimal protein folding/release activity, indicating chaperonins act as a molecular thermometer. Protein fluorescence, chemical crosslinking, kinetic analysis at different temperatures FEBS letters Medium 9166902
1998 Identification of in vivo substrates of yeast mitochondrial Hsp10 reveals that substrates fall into three groups: (i) proteins requiring both Hsp60 and Hsp10 for folding; (ii) proteins that fail to fold without Hsp60 but are unaffected by Hsp10 loss; and (iii) newly imported Hsp60 itself, which is more severely affected by Hsp10 inactivation than by pre-existing Hsp60 inactivation—demonstrating that Hsp60 and Hsp10 do not always act as a single functional unit in vivo. Novel in vivo folding screen, temperature-sensitive hsp60 and hsp10 mutants in yeast mitochondria, systematic substrate identification The EMBO journal High 9774331
1999 Pro-caspase-3 is present in the mitochondrial fraction of Jurkat T cells in a complex with Hsp60 and Hsp10. Apoptosis induction causes activation of mitochondrial pro-caspase-3 and its dissociation from the Hsps, which are released from mitochondria. In vitro, recombinant Hsp60 and Hsp10 accelerate activation of pro-caspase-3 by cytochrome c and dATP in an ATP-dependent manner, suggesting that released mitochondrial Hsps may also accelerate caspase activation in the cytoplasm. Subcellular fractionation, co-immunoprecipitation, in vitro caspase-3 activation assay with recombinant proteins, Western blotting The EMBO journal High 10205158
2001 GroEL/GroES-mediated folding of yeast mitochondrial aconitase (82 kDa, too large to be encapsulated in the cis cavity) requires both GroEL and GroES and proceeds via multiple rounds of binding and release without cis encapsulation; instead, GroES binding to the trans ring drives release, and the protein folds in solution. After refolding, GroEL stably binds apoaconitase and releases active holoenzyme upon Fe4S4 cofactor formation, independent of ATP and GroES. In vitro and in vivo folding assays, mutant GroEL analysis, biochemical fractionation Cell High 11672530
2001 Malate dehydrogenase bound to GroEL shows a core of partially protected secondary structure that is only modestly and broadly deprotected upon ATP and GroES binding, suggesting conformational change results from breaking hydrogen bonds with the cavity wall or global destabilization rather than forced mechanical unfolding ('rack' mechanism). Deuterium exchange mass spectrometry, peptic fragment analysis Nature structural biology Medium 11473265
2002 The human HSP60 (HSPD1) and HSP10 (HSPE1) genes are arranged head-to-head on chromosome 2q33.1, separated by a bidirectional promoter. The HSP60 gene has 12 exons and HSPE1 has 4 exons. The bidirectional promoter drives transcription of both genes, with heat-shock increasing promoter activity ~12-fold in either direction; transcriptional activity in the HSP60 direction is approximately twice that in the HSPE1 direction under normal conditions. Genomic sequencing, radiation hybrid mapping, luciferase reporter assay, EST analysis Human genetics High 12483302
2003 Hsp10 and Hsp60 together protect cardiomyocytes against doxorubicin-induced apoptosis by increasing Bcl-xl and Bcl-2 abundance and reducing Bax. Hsp10 and Hsp60 inhibit ubiquitination of Bcl-xl, suggesting post-translational stabilization. Hsp60 physically interacts with Bcl-xl and Bax in cardiomyocytes in vivo. Adenoviral overexpression, co-immunoprecipitation, ubiquitination assay, flow cytometry apoptosis assay, Western blotting, antisense knockdown Journal of molecular and cellular cardiology Medium 12967636
2003 Trans-only GroEL-GroES complexes (where GroES is covalently tethered to one ring, blocking substrate binding to that ring) can fold both large (aconitase) and smaller GroEL/GroES-dependent substrates (RuBisCO, malate dehydrogenase) in vitro, and rescue a GroEL-deficient bacterial strain in vivo, demonstrating that a trans mechanism involving rounds of binding to an open ring and release into bulk solution is generally productive, though less efficient than cis encapsulation for smaller substrates. In vitro folding assays, in vivo complementation of GroEL-deficient strain, trans-only GroEL-GroES constructs The EMBO journal High 12839985
2006 HSPE1 single-nucleotide variations were screened in patients with multiple mitochondrial enzyme deficiency, SIDS, and ethylmalonic aciduria; six novel variations were detected but functional investigation of promoter-region and non-synonymous coding variants indicated none had significant impact on HSP60/HSP10 function, arguing against a major role for HSPE1 variants in these diseases. DNA sequencing of HSPD1 and HSPE1 exons and promoter, functional assays of promoter variants and amino acid changes Journal of human genetics Low 17072495
2007 NO generated by iNOS in the postischemic brain downregulates HSP60 and HSP10 (HSPE1) expression via suppression of STAT3 binding to the bidirectional HSPD1/HSPE1 promoter. Reporter gene deletion and mutation studies identified the STAT3 binding site in the bidirectional promoter as responsible for LPS/IFN-γ-induced upregulation and NO-mediated downregulation of both genes. In vivo MCAO model, aminoguanidine treatment, Western blotting, luciferase reporter assay with deletion and mutation constructs, STAT3 binding site analysis Journal of neuroscience research Medium 17348040
2008 Assembly of the GroEL-GroES folding-active complex involves an intermediate allosteric state of the GroEL ring that possesses simultaneously high affinity for both GroES and non-native substrate protein, preventing substrate escape while GroES binding and substrate protein compaction takes place. Assembly involves a strategic delay in ATP hydrolysis coupled to disassembly of the old ADP-bound GroEL-GroES complex on the opposite ring. Chemically modified GroEL mutant (EL43Py) that stalls in intermediate allosteric state, FRET-based substrate encapsulation assay, kinetic analysis The Journal of biological chemistry Medium 18782766
2008 FRET monitoring shows that nearly equivalent amounts of symmetric GroEL-(GroES)2 (football-shaped) and asymmetric GroEL-GroES (bullet-shaped) complexes coexist during the functional reaction cycle in vitro; the D398A ATP hydrolysis-defective GroEL mutant forms football-shaped complexes with ATP bound to both rings; ADP prevents association of ATP to the trans ring, preventing second GroES binding. FRET with fluorescently labeled GroEL and GroES, kinetic analysis, ATPase-deficient mutant The Journal of biological chemistry Medium 18567585
2010 Lifelong overexpression of HSP10 (HSPE1) in skeletal muscle of transgenic mice prevents the age-related loss of maximum tetanic force generation and muscle cross-sectional area, and protects against contraction-induced damage, associated with protection against age-related accumulation of protein carbonyls—demonstrating a direct in vivo protective role for Hsp10 against mitochondria-linked age-related muscle decline. HSP10 transgenic mouse model, in situ muscle force measurement, contraction-induced damage protocol, protein carbonyl quantification American journal of physiology. Regulatory, integrative and comparative physiology Medium 20410481
2015 Mitochondrial Hsp70 (mtHsp70) associates with both Hsp60 and Hsp10 in the mitochondrial matrix; mtHsp70 interacts with Hsp10 independently of Hsp60; the mtHsp70-Hsp10 complex binds to unassembled Hsp60 precursor to promote its assembly into mature heptameric Hsp60 rings, revealing that Hsp10 recruits mtHsp70 to mediate biogenesis of the Hsp60 chaperonin. Comprehensive interaction study by co-immunoprecipitation and mass spectrometry, in vitro assembly assay, quantitative proteomics (SILAC) The Journal of biological chemistry High 25792736
2015 Fluorescence cross-correlation spectroscopy shows that symmetric GroEL:GroES2 (football) complexes are substantially populated only in the presence of non-foldable model proteins that over-stimulate GroEL ATPase and uncouple inter-ring negative allostery; asymmetric GroEL:GroES complexes are dominant both in the absence of substrate and with foldable substrates, and formation of symmetric complexes is suppressed at physiological ATP:ADP concentration. Fluorescence cross-correlation spectroscopy (novel assay), comparison with FRET assays, ATPase measurements Journal of molecular biology High 25912285
2016 A de novo heterozygous HSPE1 missense mutation (c.217C>T, p.Leu73Phe) identified in an infant with infantile spasms causes profound impairment of HSP10 thermal stability, spontaneous refolding propensity, and proteolytic resistance in vitro; in patient fibroblasts, mutant HSP10 protein is barely detectable, reducing the HSP10:HSP60 ratio ~2-fold and decreasing SOD2 protein (an HSP60/HSP10 client) to ~20%, with consequent ~2-fold increase in mitochondrial superoxide levels. Clinical exome sequencing, purified recombinant protein thermal stability and refolding assays, mass spectrometry quantification of patient fibroblast proteins, mitochondrial superoxide measurement, protease sensitivity assay Frontiers in molecular biosciences High 27774450
2016 Disease-causing missense mutations in HSPD1 (encoding HSP60) impair the function of the HSP60/HSP10 chaperonin complex required for protein folding in the mitochondrial matrix; different degrees of reduced HSP60 function produce distinct neurological phenotypes, and mutations with deleterious or strong dominant negative effects are not compatible with life, indicating that HSP10 (HSPE1) function is essential for HSP60-dependent mitochondrial protein folding. Complementation assays in E. coli groES groEL deletion strains, biochemical analysis of mutant proteins, patient clinical phenotype correlation Frontiers in molecular biosciences Medium 27630992
2017 The mammalian HSP60/HSP10 complex possesses GTPase activity in addition to ATPase activity; GTP affects the allostery, complex formation, and protein folding activity of HSP60/HSP10 differently from ATP, providing evidence that GTP has a distinct modulatory role in the functional mechanism of the HSP60-HSP10 complex. GTPase activity assay, protein folding assay with GTP substitution, allostery analysis Scientific reports Medium 29208924
2020 A comprehensive interaction survey of the human mitochondrial HSP60/HSP10 chaperonin using metabolic labeling, cross-linking, and immunoprecipitation of HSP60 in HEK293 cells identified 323 interacting proteins, approximately half of all annotated mitochondrial matrix proteins. The interactome covers functions including mitochondrial protein synthesis, the respiratory chain, and protein quality control; 19 abundant matrix proteins occupy more than 60% of the HSP60/HSP10 chaperonin capacity. SILAC metabolic labeling, cross-linking, HSP60 immunoprecipitation, mass spectrometry-based proteomics Cell stress & chaperones High 32060690
2021 The HSP60/HSP10 chaperonin complex is the most abundant mitochondrial protein (covering six orders of magnitude in protein abundance, amounting to 7% of cellular proteome), with half-lives spanning hours to months, indicating it is a central hub of mitochondrial protein homeostasis. Quantitative mass spectrometry-based proteomics (MitoCoP), dynamic turnover measurements Cell metabolism Medium 34800366
2024 Glutamine activates SIRT4 (by upregulating its synthesis and increasing NAD+ levels), which deacetylates HSP60, thereby facilitating assembly of the HSP60-HSP10 complex. This assembled complex maintains the activity of mitochondrial electron transport chain complexes II and III, sustaining ATP generation and reducing reactive oxygen species in burn sepsis liver injury. In vivo burn sepsis mouse model, glutamine supplementation, SIRT4 overexpression/knockdown, acetylation analysis, HSP60-HSP10 complex assembly assay, ETC complex activity measurement, ROS measurement Redox report Medium 38329114

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Biological insights from 108 schizophrenia-associated genetic loci. Nature 5878 25056061
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1997 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex. Nature 982 9285585
2005 Nucleolar proteome dynamics. Nature 934 15635413
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
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1989 The groES and groEL heat shock gene products of Escherichia coli are essential for bacterial growth at all temperatures. Journal of bacteriology 575 2563997
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
1999 Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 499 9989505
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1999 Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. The EMBO journal 438 10205158
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1992 Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. The EMBO journal 375 1361169
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
1994 Location of a folding protein and shape changes in GroEL-GroES complexes imaged by cryo-electron microscopy. Nature 314 7915827
1986 Purification and properties of the groES morphogenetic protein of Escherichia coli. The Journal of biological chemistry 303 3017973
2019 Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality. Cancer cell 298 31056398
2015 The GroEL-GroES Chaperonin Machine: A Nano-Cage for Protein Folding. Trends in biochemical sciences 292 26422689
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2002 Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. American journal of human genetics 268 11898127
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
1993 The reaction cycle of GroEL and GroES in chaperonin-assisted protein folding. Nature 257 7901770
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
1995 Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells. Molecular microbiology 230 7752884
1989 Effects of mutations in heat-shock genes groES and groEL on protein export in Escherichia coli. The EMBO journal 230 2573517
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
2012 Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 219 22810585
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2003 Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells. Journal of molecular and cellular cardiology 194 12967636
1992 Cooperation of GroEL/GroES and DnaK/DnaJ heat shock proteins in preventing protein misfolding in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 189 1359538
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