The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Identity is verified. The target is the human nuclear gene HSPD1 (Homo sapiens), encoding mitochondrial 60-kDa heat-shock protein HSP60, also called chaperonin 60 or Cpn60. This is fully consistent with UniProt P10809, the supplied precursor annotation, and membership in the GroEL/HSP60 group-I chaperonin family. The literature directly identifies HSPD1 as the gene encoding human mitochondrial HSP60; no similarly named protein from another organism was used. UniProt P10809 (rodriguez2020complexdestabilizationin pages 1-2)
HSPD1’s primary function is ATP-dependent folding of non-native proteins in the mitochondrial matrix, in cooperation with the co-chaperonin HSP10/HSPE1. It is therefore best understood as a protein-folding ATPase rather than an enzyme with one small-molecule substrate. Its clients are incompletely catalogued and are recognized principally by their non-native conformations and exposed hydrophobic surfaces. Directly supported clients include the mitochondrial ATP-synthase F1 β-subunit and malate dehydrogenase. Human HSP60 forms active single-ring HSP60₇–HSP10₇ and double-ring HSP60₁₄–(HSP10₇)₂ folding chambers (gomezllorente2020structuralbasisfor pages 1-2, wang2019mitchap60andhereditary pages 1-2).
The most firmly established clinical consequences are rare inherited chaperonopathies: dominant spastic paraplegia 13 (SPG13) and recessive hypomyelinating leukodystrophy 4/MitCHAP-60 disease. HSPD1 sequencing is clinically relevant to genetic diagnosis, but HSP60-directed drugs and circulating/tissue biomarkers remain investigational; the retrieved trial search found no relevant interventional HSPD1/HSP60 study.
| Topic | Current annotation | Best evidence | Confidence/caveat |
|---|---|---|---|
| Identity and aliases | Human HSPD1 encodes mitochondrial 60-kDa heat-shock protein HSP60, also called Cpn60/chaperonin 60. This matches UniProt P10809 and the GroEL-related group-I chaperonin family. | Human-focused literature directly identifies HSPD1 as the nuclear gene encoding mitochondrial HSP60 (Rodriguez et al., 2020) (rodriguez2020complexdestabilizationin pages 1-2). | High. No conflicting gene or organism was used. The accession comes from the supplied UniProt record; literature independently confirms the gene–protein identity. |
| Location and import | HSP60 is synthesized in the cytosol as a precursor with an N-terminal mitochondrial targeting sequence, imported into mitochondria, and proteolytically matured. Its established functional site is the mitochondrial matrix. | Import and targeting-sequence cleavage are documented in the literature summarized by Rodriguez et al. (2020); structural work directly assigns folding activity to mitochondrial-matrix proteins (Gomez-Llorente et al., 2020) (rodriguez2020complexdestabilizationin pages 1-2, gomezllorente2020structuralbasisfor pages 1-2). | High for import and matrix function. Cytosolic, cell-surface, vesicular, and extracellular HSP60 has also been reported, but its abundance, trafficking, oligomeric state, and functions outside mitochondria remain less certain (rodriguez2020complexdestabilizationin pages 3-4). |
| Structural domains | Mature HSP60 contains an equatorial ATP-binding domain at residues 1–137 and 411–526, an intermediate hinge domain at 138–191 and 375–411, and an apical client/HSP10-binding domain at 192–374. | Near-atomic human HSP60–HSP10 structures resolved these domains and showed HSP10 mobile-loop contacts with helices H and I in the apical domain (Gomez-Llorente et al., 2020) (gomezllorente2020structuralbasisfor pages 4-5). | High for the mature recombinant protein examined structurally. Residue numbers differ from full-precursor numbering because the mitochondrial targeting peptide is removed. |
| Core ATP-dependent reaction | HSP60 is an ATP-dependent protein-folding chaperonin/ATPase. It captures non-native polypeptides, encloses them in a protected cavity, uses ATP binding and hydrolysis to drive conformational changes, and releases ADP, HSP10, and folded or folding-competent client. Its supplied EC assignment is 5.6.1.7. | Human structural intermediates establish nucleotide-coupled transitions, while biochemical assays show ATP- and HSP10-dependent recovery of client activity (Gomez-Llorente et al., 2020; Wang et al., 2019) (gomezllorente2020structuralbasisfor pages 1-2, wang2019mitchap60andhereditary pages 1-2, wang2019mitchap60andhereditary pages 10-11). | High. ATP hydrolysis powers conformational work on diverse protein clients; HSP60 does not chemically modify a narrowly defined small-molecule substrate. |
| HSP10 partnership and stoichiometry | HSP60 works with co-chaperonin HSP10/HSPE1. Active assemblies include a capped single ring, HSP60₇–HSP10₇, and a double-ring football, HSP60₁₄–(HSP10₇)₂. | Cryo-EM and crystallography resolved ADP-bound half-football and ADP- or ADP·BeF₃-bound football states at 3.83, 3.08, and 3.7 Å, respectively. Footballs measured approximately 244–247 Å high and 142 Å wide; obligate single- and double-ring variants were active (Gomez-Llorente et al., 2020) (gomezllorente2020structuralbasisfor pages 2-4, gomezllorente2020structuralbasisfor pages 1-2, gomezllorente2020structuralbasisfor media d7922be4). | High. Assembly depends on nucleotide and protein concentration. Unlike bacterial GroEL, human mitochondrial HSP60 lacks equivalent negative inter-ring ATP-binding cooperativity and can productively use both ring states. |
| Substrate specificity and clients | HSP60 recognizes non-native proteins with exposed hydrophobic surfaces, making its specificity conformational rather than sequence-exclusive. Strong client evidence includes mitochondrial ATP synthase F1 β-subunit; malate dehydrogenase is a standard putative mitochondrial client and direct refolding substrate. | ATP synthase β co-immunoprecipitated with HSP60 and was refolded into an ATPase-active α₃β₃ assembly. Disease variants retained approximately 40% for V72I and 20% for D3G of wild-type β-subunit-refolding activity; corresponding α-lactalbumin results were about 35% and 12% (Wang et al., 2019) (wang2019mitchap60andhereditary pages 1-2, wang2019mitchap60andhereditary pages 10-11). | Moderate–high. Direct biochemical evidence supports these clients, but no exhaustive human-matrix client catalog or strict recognition motif is established. α-Lactalbumin is an assay substrate, not a physiological mitochondrial client. |
| Disease variants and numbering | Pathogenic HSPD1 variants cause autosomal-dominant SPG13 and autosomal-recessive hypomyelinating leukodystrophy 4/MitCHAP-60. Full-precursor notation commonly gives p.Val98Ile and p.Asp29Gly, whereas mature-protein studies use V72I and D3G. | Human genetics and biochemical studies link these variants to defective folding and altered nucleotide-coupled assembly. Open Targets reports five evidence records for each principal HSPD1-associated disease term (Wang et al., 2019; Chen et al., 2022) (OpenTargets Search: -HSPD1, wang2019mitchap60andhereditary pages 1-2, chen2022hereditaryspasticparaplegia pages 7-8). | High for disease association. Numbering caveat: D29G/D3G and V98I/V72I describe the same substitutions using precursor versus mature numbering. V72I can increase ATPase activity yet reduce productive folding, showing that ATP turnover alone does not measure chaperonin efficacy. |
| Pathways and stress response | HSPD1 is a mitochondrial-proteostasis effector associated with mitochondrial unfolded-protein response and integrated-stress-response programs involving ATF4, ATF5, and CHOP. Its primary role is to increase matrix folding capacity rather than act as the upstream stress sensor. | A 2024 review integrates mammalian UPRmt evidence and HSP60 regulation (Zhang et al., 2024); human stress-response research has used genome-scale perturbation approaches to dissect mtISR regulators (mayer2024geneticregulationofa pages 1-7). Extra-mitochondrial studies also implicate HSP60 in IKK/NF-κB, ERK/MAPK, and TLR4 signaling (rodriguez2020complexdestabilizationin pages 3-4). | High for matrix proteostasis, moderate for exact human UPRmt transcriptional wiring, and lower for proposed extracellular signaling, where localization and context require careful validation. |
| Applications and clinical status | Current uses are chiefly research, molecular genetic diagnosis, experimental biomarker evaluation, and preclinical target discovery. HSP60 modulators have been investigated for cancer, inflammatory disease, and autoimmunity; stabilization strategies are conceptually relevant to loss-of-function chaperonopathies. | Reported chemical modulators generally have low-micromolar to millimolar potency (Meng et al., 2018) (meng2018towarddevelopingchemical pages 1-2). The retrieved clinical-trial search identified no relevant interventional HSPD1/HSP60 trial; disease-target resources support genetic associations rather than an approved drug mechanism (OpenTargets Search: -HSPD1). | Low–moderate translational maturity. No HSPD1-directed drug, companion diagnostic, or HSP60 biomarker identified here is clinically validated or approved. Broad inhibition poses safety concerns because mitochondrial HSP60 is essential for proteostasis. |
Table: Compact functional-annotation evidence for human HSPD1/UniProt P10809, separating direct structural, biochemical, and genetic findings from inference. It highlights precursor-versus-mature variant numbering and the absence of validated HSPD1-directed clinical therapies.
The supplied gene symbol, organism, and protein description are mutually consistent:
A nomenclature issue is important in interpreting pathogenic variants. Human HSP60 is synthesized with an N-terminal mitochondrial targeting peptide that is removed after import. Consequently, papers using full precursor numbering refer to p.Asp29Gly and p.Val98Ile, whereas biochemical studies of the mature chain frequently use D3G and V72I, respectively. These are not separate variants (wang2019mitchap60andhereditary pages 1-2, chen2022hereditaryspasticparaplegia pages 7-8).
HSPD1 is nuclear encoded and translated on cytosolic ribosomes as a precursor. Its N-terminal targeting sequence directs import into mitochondria and is cleaved during translocation. The mature chaperonin operates predominantly in the mitochondrial matrix, where many nuclear-encoded proteins arrive in unfolded or incompletely folded states and require productive folding after import (rodriguez2020complexdestabilizationin pages 1-2, gomezllorente2020structuralbasisfor pages 1-2).
A smaller pool has been reported in the cytosol, nucleus, cell surface, extracellular vesicles, extracellular space, and blood. Proposed extra-mitochondrial activities include modulation of IKK/NF-κB, ERK/MAPK and TLR4 signaling and immune recognition. These observations should not be conflated with the primary annotation: abundance is generally low, trafficking mechanisms are incompletely defined, and it remains uncertain whether extra-mitochondrial HSP60 functions as monomers or canonical oligomeric folding machines (rodriguez2020complexdestabilizationin pages 3-4). Thus, mitochondrial-matrix proteostasis is the high-confidence functional location; extracellular signaling is context-dependent and less mechanistically secure.
Structures of mature human HSP60 resolve three domains:
HSP10 forms a heptameric dome. Its approximately 20-residue mobile loops contact helices H and I in the HSP60 apical domains, closing the chamber over the client. The flexible HSP60 C-terminal tails project toward the cavity and may influence the internal folding environment (gomezllorente2020structuralbasisfor pages 5-6, gomezllorente2020structuralbasisfor pages 4-5).
The strongest human structural study resolved three reaction-cycle states: an ADP·BeF₃ ATP-ground-state mimic HSP60₁₄–(HSP10₇)₂ football at 3.7 Å, an ADP football at 3.08 Å, and an ADP HSP60₇–HSP10₇ half-football at 3.83 Å. The double-ring particles were about 244–247 Å high and 142 Å wide; the single-ring complex was also approximately 142 Å wide (gomezllorente2020structuralbasisfor pages 2-4, gomezllorente2020structuralbasisfor media d7922be4). In the cryo-EM sample, football and half-football particles constituted approximately 70% and 30%, respectively (gomezllorente2020structuralbasisfor pages 1-2).
The supplied EC assignment, EC 5.6.1.7, describes an ATP-dependent protein-folding chaperone. A concise functional reaction is:
non-native client protein + ATP + H₂O → folded/folding-competent client protein + ADP + phosphate, mediated by HSP60–HSP10 conformational cycling.
This is not covalent catalysis of the client. ATP hydrolysis drives reversible changes in chamber assembly, client encapsulation, and release. HSP60 lowers kinetic barriers to productive folding and suppresses aggregation by isolating a client in a protected nanocage (rodriguez2020complexdestabilizationin pages 1-2, gomezllorente2020structuralbasisfor pages 1-2).
Current evidence supports the following cycle:
Unlike E. coli GroEL, human mitochondrial HSP60 does not show the same negative ATP-binding cooperativity between rings. Both single- and double-ring variants are active, and a forced single-ring variant complemented bacterial chaperonin deficiency about as efficiently as wild-type human HSP60. Thus, the single ring is not merely a breakdown product; it is a productive intermediate (gomezllorente2020structuralbasisfor pages 1-2).
HSP60 has broad conformational specificity, not a narrow sequence motif or one chemically defined substrate. It preferentially recognizes exposed hydrophobic patches characteristic of incompletely folded or stress-denatured proteins. Its physiological client set is expected to include imported and stress-damaged matrix proteins, particularly proteins needed for mitochondrial metabolism, but a definitive human client census is not yet available (rodriguez2020complexdestabilizationin pages 1-2).
The most informative precise substrate evidence concerns mitochondrial ATP synthase:
Malate dehydrogenase is a widely used putative mitochondrial client and was directly refolded in ATP/HSP10-dependent assays. α-Lactalbumin is also used experimentally, but it should be regarded as a generic assay substrate rather than a physiological matrix client. In Wang et al., V72I and D3G retained approximately 35% and 12%, respectively, of wild-type α-lactalbumin-refolding activity; DLS showed nucleotide-induced mutant-complex contraction/dissociation from roughly 16 nm to 9 nm (wang2019mitchap60andhereditary pages 10-11, wang2019mitchap60andhereditary pages 9-10).
HSPD1 acts downstream of mitochondrial import: precursor proteins cross mitochondrial membranes and are then folded into active conformations with assistance from matrix chaperones, including the HSP60–HSP10 system. This function supports respiratory-chain and ATP-production pathways indirectly by ensuring that their constituent proteins achieve stable, active structures (rodriguez2020complexdestabilizationin pages 1-2, wang2019mitchap60andhereditary pages 1-2).
HSPD1 is commonly treated as a core mitochondrial unfolded-protein response (UPRmt)/mitochondrial integrated stress response effector. Matrix proteotoxic stress activates cytosolic transcriptional programs involving ATF4, ATF5, and CHOP, increasing chaperone and protease capacity. HSPD1 is therefore primarily part of the response’s folding machinery, not established as its initiating sensor. Human pathway architecture remains less linear and less completely defined than the canonical ATFS-1 pathway in C. elegans; recent human work has emphasized DELE1-dependent stress relay and genome-wide identification of mtISR regulators (mayer2024geneticregulationofa pages 1-7).
Two 2024 reviews—Singh et al., published May 2024 (DOI), and Zhang et al., published September 2024 (DOI)—place HSP60 among the proteostasis effectors induced in mammalian mitochondrial stress and emphasize its emerging importance in cancer adaptation. Their translational conclusions are mainly synthesis and hypothesis generation, rather than evidence of an approved HSPD1 therapy.
Failure of HSP60 activity is expected to produce aggregation or degradation of matrix clients, impaired respiratory-complex and ATP-synthase function, energetic stress, and secondary activation of cell-death or stress pathways. High-energy tissues—long corticospinal axons, myelinating cells, muscle, and heart—are particularly vulnerable. This model is supported by variant refolding defects and loss-of-function animal phenotypes but should not be interpreted as proof that every reported HSPD1-associated phenotype results exclusively from ATP-synthase β-subunit misfolding (rodriguez2020complexdestabilizationin pages 3-4, wang2019mitchap60andhereditary pages 1-2).
Dominant HSPD1-associated hereditary spastic paraplegia presents principally with progressive lower-extremity spasticity, weakness, gait disturbance, and corticospinal-tract degeneration. The classic substitution is full-precursor p.Val98Ile, corresponding to mature-chain V72I (rodriguez2020complexdestabilizationin pages 3-4, wang2019mitchap60andhereditary pages 1-2).
Mechanistically, V72I lies near the equatorial nucleotide-binding region and uncouples ATP turnover from productive folding. Earlier experiments found nucleotide-dependent oligomer destabilization and reduced client folding. Chen et al. subsequently reported that V72I could be more structurally stable and have greater ATPase activity than wild type while remaining less efficient at MDH folding and failing bacterial complementation at 42 °C. These apparently divergent findings reinforce an important conclusion: neither oligomer abundance nor high ATPase activity alone guarantees productive chaperone function; correctly timed allosteric dynamics are essential. Chen et al., published October 2022: DOI (chen2022hereditaryspasticparaplegia pages 7-8).
Recessive full-precursor p.Asp29Gly, mature D3G, causes a severe early-onset hypomyelinating leukodystrophy, also termed MitCHAP-60 disease or a Pelizaeus–Merzbacher-like disorder. Reported manifestations include developmental delay, nystagmus, weakness, spasticity, diffuse hypomyelination and, in severe cases, death within the first two decades. D3G produces more severe biochemical loss of folding than V72I in several assays and destabilizes nucleotide-bound complexes (wang2019mitchap60andhereditary pages 1-2, wang2019mitchap60andhereditary pages 9-10).
Curated Open Targets results independently identify HSPD1 as the sole associated target returned for hereditary spastic paraplegia 13 and hypomyelinating leukodystrophy 4, with five evidence records for each queried disease entry. These counts describe database evidence items, not prevalence or patient numbers (OpenTargets Search: -HSPD1).
Recent literature has primarily advanced the systems context of HSPD1 rather than overturning its core molecular annotation:
The clearest real-world application is molecular diagnosis: HSPD1 should be included in sequencing and variant interpretation for unexplained pure hereditary spastic paraplegia and severe early-onset hypomyelinating leukodystrophy/Pelizaeus–Merzbacher-like presentations. Functional interpretation must account for precursor-versus-mature numbering and should assess productive refolding, not ATPase activity alone.
HSP60 abundance has been investigated in tissue, plasma, and extracellular vesicles in cancer, inflammation, atherosclerosis, epilepsy, and infection. These studies demonstrate detectability and disease association but not adequate disease specificity, standardized thresholds, or prospective clinical utility. HSP60 is a ubiquitous stress protein, so an elevation can reflect generalized mitochondrial or cellular injury rather than a disease-specific mechanism (meng2018towarddevelopingchemical pages 1-2, rodriguez2020complexdestabilizationin pages 3-4).
Natural and synthetic inhibitors—including mizoribine, epolactaene-related compounds, myrtucommulone, stephacidin/avrainvillamide analogues, carboranyl compounds, and gold porphyrins—have been explored. Reported potency generally spans low-micromolar to millimolar concentrations, and proposed uses include cancer, inflammation, and autoimmunity. These are preclinical chemical probes or leads, not approved HSPD1 drugs (meng2018towarddevelopingchemical pages 1-2).
Therapeutic strategy is intrinsically difficult. Broad inhibition may damage normal cells because HSP60 is essential for mitochondrial proteostasis; conversely, inherited loss-of-function disorders would logically require restoration or stabilization rather than inhibition. Selectivity over bacterial GroEL and delivery to the mitochondrial matrix are additional pharmacological challenges. No HSPD1-directed drug, companion diagnostic, or validated HSP60 biomarker was identified as approved, and the retrieved clinical-trial search yielded no relevant interventional HSPD1/HSP60 trial.
References
(rodriguez2020complexdestabilizationin pages 1-2): Alejandro Rodriguez, Daniel Von Salzen, Bianka A. Holguin, and Ricardo A. Bernal. Complex destabilization in the mitochondrial chaperonin hsp60 leads to disease. Frontiers in Molecular Biosciences, Jul 2020. URL: https://doi.org/10.3389/fmolb.2020.00159, doi:10.3389/fmolb.2020.00159. This article has 35 citations.
(gomezllorente2020structuralbasisfor pages 1-2): Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, and Iban Ubarretxena-Belandia. Structural basis for active single and double ring complexes in human mitochondrial hsp60-hsp10 chaperonin. Nature Communications, Apr 2020. URL: https://doi.org/10.1038/s41467-020-15698-8, doi:10.1038/s41467-020-15698-8. This article has 93 citations and is from a highest quality peer-reviewed journal.
(wang2019mitchap60andhereditary pages 1-2): Jinliang Wang, Adrian S. Enriquez, Jihui Li, Alejandro Rodriguez, Bianka Holguin, Daniel Von Salzen, Jay M. Bhatt, and Ricardo A. Bernal. Mitchap-60 and hereditary spastic paraplegia spg-13 arise from an inactive hsp60 chaperonin that fails to fold the atp synthase β-subunit. Scientific Reports, Aug 2019. URL: https://doi.org/10.1038/s41598-019-48762-5, doi:10.1038/s41598-019-48762-5. This article has 27 citations and is from a peer-reviewed journal.
(rodriguez2020complexdestabilizationin pages 3-4): Alejandro Rodriguez, Daniel Von Salzen, Bianka A. Holguin, and Ricardo A. Bernal. Complex destabilization in the mitochondrial chaperonin hsp60 leads to disease. Frontiers in Molecular Biosciences, Jul 2020. URL: https://doi.org/10.3389/fmolb.2020.00159, doi:10.3389/fmolb.2020.00159. This article has 35 citations.
(gomezllorente2020structuralbasisfor pages 4-5): Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, and Iban Ubarretxena-Belandia. Structural basis for active single and double ring complexes in human mitochondrial hsp60-hsp10 chaperonin. Nature Communications, Apr 2020. URL: https://doi.org/10.1038/s41467-020-15698-8, doi:10.1038/s41467-020-15698-8. This article has 93 citations and is from a highest quality peer-reviewed journal.
(wang2019mitchap60andhereditary pages 10-11): Jinliang Wang, Adrian S. Enriquez, Jihui Li, Alejandro Rodriguez, Bianka Holguin, Daniel Von Salzen, Jay M. Bhatt, and Ricardo A. Bernal. Mitchap-60 and hereditary spastic paraplegia spg-13 arise from an inactive hsp60 chaperonin that fails to fold the atp synthase β-subunit. Scientific Reports, Aug 2019. URL: https://doi.org/10.1038/s41598-019-48762-5, doi:10.1038/s41598-019-48762-5. This article has 27 citations and is from a peer-reviewed journal.
(gomezllorente2020structuralbasisfor pages 2-4): Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, and Iban Ubarretxena-Belandia. Structural basis for active single and double ring complexes in human mitochondrial hsp60-hsp10 chaperonin. Nature Communications, Apr 2020. URL: https://doi.org/10.1038/s41467-020-15698-8, doi:10.1038/s41467-020-15698-8. This article has 93 citations and is from a highest quality peer-reviewed journal.
(gomezllorente2020structuralbasisfor media d7922be4): Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, and Iban Ubarretxena-Belandia. Structural basis for active single and double ring complexes in human mitochondrial hsp60-hsp10 chaperonin. Nature Communications, Apr 2020. URL: https://doi.org/10.1038/s41467-020-15698-8, doi:10.1038/s41467-020-15698-8. This article has 93 citations and is from a highest quality peer-reviewed journal.
(OpenTargets Search: -HSPD1): Open Targets Query (-HSPD1, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(chen2022hereditaryspasticparaplegia pages 7-8): Lingling Chen, Aiza Syed, and Adhitya Balaji. Hereditary spastic paraplegia spg13 mutation increases structural stability and atpase activity of human mitochondrial chaperonin. Scientific Reports, Oct 2022. URL: https://doi.org/10.1038/s41598-022-21993-9, doi:10.1038/s41598-022-21993-9. This article has 12 citations and is from a peer-reviewed journal.
(mayer2024geneticregulationofa pages 1-7): EME Mayer. Genetic regulation of the mitochondrial integrated stress response in humans. Unknown journal, 2024.
(meng2018towarddevelopingchemical pages 1-2): Qianli Meng, Bingbing X. Li, and Xiangshu Xiao. Toward developing chemical modulators of hsp60 as potential therapeutics. Frontiers in Molecular Biosciences, Apr 2018. URL: https://doi.org/10.3389/fmolb.2018.00035, doi:10.3389/fmolb.2018.00035. This article has 147 citations.
(gomezllorente2020structuralbasisfor pages 5-6): Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, and Iban Ubarretxena-Belandia. Structural basis for active single and double ring complexes in human mitochondrial hsp60-hsp10 chaperonin. Nature Communications, Apr 2020. URL: https://doi.org/10.1038/s41467-020-15698-8, doi:10.1038/s41467-020-15698-8. This article has 93 citations and is from a highest quality peer-reviewed journal.
(rodriguez2020complexdestabilizationin pages 2-3): Alejandro Rodriguez, Daniel Von Salzen, Bianka A. Holguin, and Ricardo A. Bernal. Complex destabilization in the mitochondrial chaperonin hsp60 leads to disease. Frontiers in Molecular Biosciences, Jul 2020. URL: https://doi.org/10.3389/fmolb.2020.00159, doi:10.3389/fmolb.2020.00159. This article has 35 citations.
(wang2019mitchap60andhereditary pages 9-10): Jinliang Wang, Adrian S. Enriquez, Jihui Li, Alejandro Rodriguez, Bianka Holguin, Daniel Von Salzen, Jay M. Bhatt, and Ricardo A. Bernal. Mitchap-60 and hereditary spastic paraplegia spg-13 arise from an inactive hsp60 chaperonin that fails to fold the atp synthase β-subunit. Scientific Reports, Aug 2019. URL: https://doi.org/10.1038/s41598-019-48762-5, doi:10.1038/s41598-019-48762-5. This article has 27 citations and is from a peer-reviewed journal.