Hsp78 chaperone complex

cellstructuremech:hsp78_chaperone_complex · Other · Multiprotein complex · Proposed

An oligomeric mitochondrial matrix chaperone assembly built from Hsp78-type subunits and involved in ATP-dependent solubilization of aggregated proteins. [DOI:10.1016/j.jbc.2022.102494]

Image (not hosted — OTHER): PMC9574514.1 fig1

Yeast Hsp78 construct, expression, purified-protein ATPase, post-heat growth and oligomerization assays. BN-PAGE and SEC support oligomeric preparations, not an atomic structure or universal subunit count. The recombinant assays use bacterially expressed yeast protein. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Witold Jaworek, Marc Sylvester, Giovanna Cenini and Wolfgang Voos (2022), Figure 1, DOI 10.1016/j.jbc.2022.102494; CC BY-NC-ND 4.0. · OTHER · source: PMC PMC9574514.1 fig1 · DOI:10.1016/j.jbc.2022.102494

Part of: mitochondrial matrix (GO:0005759)

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Stoichiometry	Essential	Role
Hsp78-type chaperone subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	HSP78			ATPase chaperone subunit forming mitochondrial Hsp78 oligomers. The curated yeast preparations show multiple oligomeric states, so no invariant copy number is assigned. `DOI:10.1016/j.jbc.2022.102494` Figure 1E and Results report Hsp78-containing oligomers after digitonin solubilization of isolated yeast mitochondria. Figure 1F analyzes purified bacterially expressed yeast protein by size-exclusion chromatography. Neither assay is an atomic structure or a time-resolved assembly pathway. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P33416/?page_size=200` Native combined endpoint inspected 2026-10-05: nine integrated matches, next=null. IPR001270 and IPR050130 are broader ClpA/B families; four domains, two conserved sites and one homologous superfamily are not exact Hsp78 family identities. This bounded result motivates label-only grounding, not a claim that every possible authority lacks an exact term.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Hsp78-type chaperone subunit

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P33416`	Heat shock protein 78, mitochondrial	HSP78	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (1 reference) Reviewed reference sequence for the mitochondrial chaperone subunit, not an identifier for the whole oligomer or the experimental strain. `UniProtKB:P33416` Native reviewed entry verifies HSP78, YDR258C, YD9320A.08C, reference taxon and matrix localization. Its homohexamer annotation does not establish a fixed copy number in every preparation.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Yeast Hsp78 oligomerization and disaggregation experiments. Methods identify Y03617-ES for non-qMS work and Y13617-ES for qMS; the experimental strains are not silently equated with S288C. Recombinant protein assays use E. coli as an expression host, not as the native organism for this structure. [DOI:10.1016/j.jbc.2022.102494]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence organism of the reviewed Hsp78 example; this does not reassign the paper's experimental strains. [UniProtKB:P33416]

Functions

ATP-dependent protein disaggregase activity GO:0140545 — Supports resolubilization of heat-aggregated reporter protein in isolated yeast mitochondria. Recovery into a soluble fraction is not itself evidence of refolding or restored reporter enzymatic activity.
- DOI:10.1016/j.jbc.2022.102494 Figure 2 compares recovery of imported radiolabeled b2(107)Delta-DHFRDS reporter in wild-type-complemented, Hsp78TR, deletion and ATP-depleted mitochondria. Organelle-wide ATP depletion is not an Hsp78-specific intervention.
- UniProtKB:P33416 Reviewed annotation supports ATP-dependent disaggregation and functional cooperation with mitochondrial Hsp70; cooperation does not imply a fixed heteromeric composition.
ATP hydrolysis activity GO:0016887 — ATPase activity of Hsp78, measured with purified recombinant yeast protein.
- DOI:10.1016/j.jbc.2022.102494 Figure 1C measures phosphate release with 0.08 microgram/microliter protein and 0.25 mM ATP at 37 C. The Hsp78TR construct retains residual activity and is not ATPase-null.

Mechanism graphs

Yeast Hsp78 oligomer membership and assay-bounded interventions (FUNCTION)

Hsp78 membership, purified-protein ATPase activity, mitochondrial reporter resolubilization and post-heat growth assays.

Subject	Predicate	Object	Evidence
Hsp78-type chaperone subunit	forms	Hsp78 chaperone complex	`DOI:10.1016/j.jbc.2022.102494` Figure 1E-F supports oligomeric Hsp78 preparations; native-gel migration was interpreted as trimeric and hexameric species, without a universal copy count.
Hsp78 chaperone complex	catalyzes	ATP hydrolysis activity	`DOI:10.1016/j.jbc.2022.102494` Figure 1C measures ATP-dependent phosphate release from purified Hsp78. The active oligomeric state was not independently assigned for each assay point.
Purified recombinant Hsp78TR assay preparation	impairs	ATP hydrolysis activity	`DOI:10.1016/j.jbc.2022.102494` Figure 1C reports approximately 70 percent lower ATPase activity of purified Hsp78TR than WT, not complete loss.
Hsp78TR complementation	impairs	Recovery of soluble mitochondrial DHFR reporter	`DOI:10.1016/j.jbc.2022.102494` Figure 2A-C shows reduced reporter recovery in Hsp78TR mitochondria relative to WT complementation. This does not isolate ATP hydrolysis from substrate binding, expression or assembly changes.
HSP78 deletion	impairs	Recovery of soluble mitochondrial DHFR reporter	`DOI:10.1016/j.jbc.2022.102494` Figure 2A-C shows reduced reporter resolubilization in hsp78 deletion mitochondria under the specified heat/recovery conditions.
Hsp78WT complementation	restores relative to deletion	Recovery of soluble mitochondrial DHFR reporter	`DOI:10.1016/j.jbc.2022.102494` Figure 2A-C shows improved recovery with Hsp78WT complementation, not quantitative recovery of all substrate or demonstration of restored DHFR activity.
Hsp78TR complementation	impairs	Growth on glycerol after acquired-thermotolerance treatment	`DOI:10.1016/j.jbc.2022.102494` Figure 1D compares serial dilutions on glucose and glycerol after 60 minutes at 42 C, a 30-minute 30 C regeneration step specified in Methods, and 60 minutes at 48 C. TR impairs subsequent growth on glycerol relative to WT complementation; glucose growth is similar. No direct respiration or universal heat-survival claim is inferred.

Discussions

INTERPRETATION (RESOLVED): Separate the Hsp78 oligomer from its subunit, cooperating chaperones and potential clients. Hsp78 is one gene product but forms a distinct mitochondrial oligomer. Copurification does not establish invariant structural membership.
CURATION_TODO (OPEN): Resolve an exact source-neutral Hsp78-type component family if an authority supplies one. The nine integrated InterPro matches for reviewed P33416 include broader ClpA/B families, domains and sites; using those as an exact Hsp78 identity would overstate specificity.
CURATION_TODO (OPEN): Resolve preparation-dependent oligomeric states and source-internal construct/protocol discrepancies before asserting a fixed copy number or residue-specific mechanism. Figure 1A and Results give E216Q/E614Q for Hsp78TR, whereas Methods give E612Q for the second substitution. High-salt SEC is described with NaCl in Results and KCl in Methods, and the compared buffers also differ in ATP and magnesium. Figure 2D and Methods differ in aggregation and centrifugation conditions.
INTERPRETATION (RESOLVED): Separate purified recombinant Hsp78TR assays from yeast complementation in the causal graph. The initial graph reused a state labelled Hsp78TR complementation for an ATPase assay performed on bacterially expressed purified protein. Correct edge notes did not repair the mismatched intervention subject.

More images

Image (not hosted — OTHER): PMC9574514.1 fig2

Heat-aggregated mitochondrial DHFR reporter recovery and Hsp78 aggregate cosedimentation. Soluble-fraction recovery is distinct from restored enzymatic function; the binding experiment is a separate assay. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Witold Jaworek, Marc Sylvester, Giovanna Cenini and Wolfgang Voos (2022), Figure 2, DOI 10.1016/j.jbc.2022.102494; CC BY-NC-ND 4.0. · OTHER · source: PMC PMC9574514.1 fig2 · DOI:10.1016/j.jbc.2022.102494

Datasets

Hsp78 heat-stress proteomics: Part A, protein interactions (PXD030405) · PRIDE · PROTEOMICS
Organism: Saccharomyces cerevisiae (NCBITaxon:4932) · Platform: SILAC LC-MS/MS with an LTQ Orbitrap Velos
Enrichment identifies potential interactors, not fixed stoichiometric subunits or binding-affinity constants.
Native PRIDE API verified accession, yeast taxon, paired project, publication DOI, instrument and CC0 dataset licence on 2026-10-05. Archive publication PMID is zero, so it is not used as a PMID assertion. Raw mass-spectrometry files were not downloaded or reanalyzed. Dataset CC0 does not change the paper figures' CC BY-NC-ND 4.0 licence.
- https://www.ebi.ac.uk/pride/archive/projects/PXD030405 Native project metadata matches the primary paper Data availability assignment.
Hsp78 heat-stress proteomics: Part B, aggregation (PXD030436) · PRIDE · PROTEOMICS
Organism: Saccharomyces cerevisiae (NCBITaxon:4932) · Platform: SILAC LC-MS/MS with an LTQ Orbitrap Velos
Condition-dependent changes in protein sedimentation support a role in proteostasis; pellet recovery is not direct proof of refolding, physiological client identity or complete disaggregation.
Native PRIDE API verified accession, yeast taxon, paired project, publication DOI, instrument and CC0 dataset licence on 2026-10-05. Archive publication PMID is zero, so it is not used as a PMID assertion. Raw mass-spectrometry files were not downloaded or reanalyzed. Dataset CC0 does not change the paper figures' CC BY-NC-ND 4.0 licence.
- https://www.ebi.ac.uk/pride/archive/projects/PXD030436 Native project metadata matches the primary paper Data availability assignment.

Evidence

DOI:10.1016/j.jbc.2022.102494 Jaworek, Sylvester, Cenini and Voos (2022), PMID 36115461. Read abstract, Results, Discussion, Methods, Data availability and main-figure captions in PMC9574514.1; actual Figures 1 and 2 inspected. XML SHA-256 75b5f2c13addf3554fbd534e58fea2aa26605afe26987185a88cc7b3c9a5b2d8. Older oligomer studies cited by the authors were not fully accessible and are not independently treated as inspected evidence.
UniProtKB:P33416 Native reviewed entry supplies matrix location, reference identity and enzyme annotation.
GO:0101031 Verified active cellular-component term protein folding chaperone complex; broader parent, not exact identity.
GO:0005759 Verified active cellular-component term mitochondrial matrix; compartment parthood, not is-a parentage.

Curation history

2026-10-05T02:53:34Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T02:55:21Z codex · EXPANDED_RECORD — Added yeast-scoped Hsp78 assembly composition, reviewed reference protein, assay-bounded function graph, verified PRIDE datasets, link-only licensed figures and explicit source conflicts.
2026-10-05T03:19:42Z codex · CURATED_CAUSAL_GRAPH — Addressed PR 2049 review issues 2050 and 2051: separated purified-protein and yeast-complementation graph states and attached native InterPro evidence without changing biological scope or label-only grounding.

Source: data/structures/other/hsp78_chaperone_complex.yaml