protein aggregate center

GO:0140453 · Inclusion · Inclusion body · Proposed

A reversible intracellular assembly of misfolded proteins and chaperones that temporarily protects heat-sensitive clients from degradation and can be disassembled when conditions permit recovery. [GO:0140453]

Figure 2. GFP-tagged Hsp42, Hsp104 and Btn2 form heat-induced foci in BY4741-derived budding yeast at 37 C. Rows compare the tagged chaperones over time; dashed outlines mark cells and scale bars are 5 micrometers. Hsp104 is a disaggregase, not a small heat shock protein. Separate single-label images do not establish simultaneous three-way colocalization. FLUORESCENCE · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Susanna Boronat, Margarita Cabrera, Montserrat Vega, Jorge Alcalá, Silvia Salas-Pino, Rafael R. Daga, José Ayté, Elena Hidalgo; CC BY, via PubMed Central · CC_BY_4_0 · source: PMC PMC10342647.1 ijms-24-11202-f002 · `DOI:10.3390/ijms241311202`

Synonyms: protein aggregate centre; PAC; protein aggregate-like center

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

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
heterogeneous misfolded protein cargo	Other	part of	Reviewed label only (reviewed name; no accession asserted)		UNKNOWN	Reversibly sequestered heat-sensitive protein material. Rho1.C17R-GFP and Guk1-9-GFP are engineered probes of this cargo, not invariant native subunits. `DOI:10.3390/ijms241311202` Results 2.1-2.4 and Figures 1, 3 and 6 track reporter deposition, persistence and turnover.
Small heat shock protein	Protein	part of	`InterPro:IPR031107`	HSP42	UNKNOWN	Deposited chaperone class exemplified by Hsp42 in budding yeast. Joint loss of Hsp42 and Btn2 impairs reporter PAC formation or persistence; residual foci depend on reporter and strain. This combined perturbation does not establish a universal single-protein or family-wide requirement. `DOI:10.3390/ijms241311202` Results 2.1-2.2 and Figures 2-3 support residence and context-dependent joint deletion effects. `InterPro:IPR031107` Complete native integrated match set has three entries; IPR031107 is the family, while the other matches are a domain and a homologous superfamily.
Btn2-type aggregase	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	BTN2	CONDITIONAL	PAC-enriched sorting factor whose formation and maintenance effects depend on substrate, genetic background and stress intensity. Results 2.2 reports that BTN2 loss blocks the Rho1 reporter PACs in W303, but other reporters/backgrounds retain foci; this is not universal essentiality. `DOI:10.3390/ijms241311202` Results 2.1-2.2 and Figures 2-3 distinguish localization, single deletions and joint loss. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P53286/?page_size=200` One native integrated match, next=null; domain-only grounding declined.
Hsp104-type disaggregase	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP104	DISPENSABLE	Focus-associated disaggregase that supports PAC clearance during recovery and prolonged heat stress. Reporter PACs still form without Hsp104. Disappearance of fluorescent foci alone is not proof of client degradation. `DOI:10.3390/ijms241311202` Results 2.3 and Figure 4 show PACs in deletion cells and delayed clearance; recovery uses CHX after assembly. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P31539/?page_size=200` Complete native integrated match set checked through next=null.

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.

Small heat shock protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:Q12329`	Heat shock protein 42	HSP42	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example, not a reassignment of W303 or BY4741 experimental backgrounds to S288C. Figure 2 shows Hsp42-GFP foci in BY4741; Figure 3 tests joint BTN2/HSP42 deletion. `UniProtKB:Q12329` Native reviewed entry verifies accession, name, gene and reference taxon. `DOI:10.3390/ijms241311202` Figure 2 shows Hsp42-GFP foci in BY4741; Figure 3 tests joint BTN2/HSP42 deletion.

Btn2-type aggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P53286`	Protein BTN2	BTN2	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example, not a reassignment of W303 or BY4741 experimental backgrounds to S288C. Figure 2 shows Btn2-GFP foci; Results 2.2 separates single-deletion observations from the double-deletion assays in Figure 3. `UniProtKB:P53286` Native reviewed entry verifies accession, name, gene and reference taxon. `DOI:10.3390/ijms241311202` Figure 2 shows Btn2-GFP foci; Results 2.2 separates single-deletion observations from the double-deletion assays in Figure 3.

Hsp104-type disaggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P31539`	Heat shock protein 104	HSP104	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example, not a reassignment of W303 or BY4741 experimental backgrounds to S288C. Figures 2 and 4 show focus association and separate PAC formation from Hsp104-dependent clearance. `UniProtKB:P31539` Native reviewed entry verifies accession, name, gene and reference taxon. `DOI:10.3390/ijms241311202` Figures 2 and 4 show focus association and separate PAC formation from Hsp104-dependent clearance.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — W303 and BY4741 derivatives form reporter PACs at 37 C, with different persistence and genetic requirements. Figure 2 images BY4741-derived GFP-tagged chaperones. These are experimental examples, not clade-wide prevalence. [DOI:10.3390/ijms241311202]
NCBITaxon:4896 Schizosaccharomyces pombe — Figure 1c includes strain 972 in the same Rho1.C17R-GFP heat-shock comparison. Mild-stress fission-yeast PAC localization is not assumed identical to budding-yeast nuclear and cytoplasmic foci. [DOI:10.3390/ijms241311202]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence taxon for the reviewed protein examples; not a reassignment of every source assay or imaged cell to this strain. [UniProtKB:Q12329]

Functions

temporary sequestration of heat-sensitive protein clients — Collects misfolding-prone proteins in heat-induced foci. The same reporters persist differently in fission yeast, W303 and BY4741; a fixed lifetime is not part of the structure identity.
- DOI:10.3390/ijms241311202 Results 2.1 and Figure 1 compare reporter PAC formation and persistence.
postponement of client degradation — PAC deposition can delay degradation of the tested misfolding reporters. Recovery permits disassembly, whereas prolonged heat can be followed by turnover. The study's folding-versus-degradation model is not proof that every endogenous client follows one fate.
- DOI:10.3390/ijms241311202 Results 2.3-2.4 and Figures 4-6 combine deletion, translation inhibition and immunoblot measurements; Figure 6d summarizes the proposed routing model.

Mechanism graphs

Reporter PAC formation during mild heat stress (ASSEMBLY)

Subject	Predicate	Object	Evidence
Temperature shift to 37 C	induces	protein aggregate center	`DOI:10.3390/ijms241311202` Results 2.1 and Figure 1c.
Joint BTN2 and HSP42 deletion	impairs	protein aggregate center	`DOI:10.3390/ijms241311202` Results 2.2 and Figure 3, not an inferred identical single-deletion effect.
Cycloheximide present during 37 C induction	blocks	protein aggregate center	`DOI:10.3390/ijms241311202` Results 2.4 and Figure 6a; Discussion distinguishes severe heat.

Perturbations of PAC deposition and reporter turnover (FUNCTION)

Subject	Predicate	Object	Evidence
Joint BTN2 and HSP42 deletion	accelerates	Misfolding-reporter degradation	`DOI:10.3390/ijms241311202` Results 2.4 and Figure 6c; reduced PAC persistence accompanies faster turnover.
Cycloheximide at 37 C	accelerates	Misfolding-reporter degradation	`DOI:10.3390/ijms241311202` Results 2.4 and Figure 6b provide the temperature control.

Hsp104-dependent PAC clearance (DISASSEMBLY)

Subject	Predicate	Object	Evidence
Return to 25 C after PAC assembly, with CHX	permits	Reporter PAC clearance during recovery	`DOI:10.3390/ijms241311202` Results 2.3 and Figure 4b; focus disappearance is not equated with proteolysis.
HSP104 deletion	impairs	Reporter PAC clearance during recovery	`DOI:10.3390/ijms241311202` Results 2.3 and Figure 4b.
HSP104 deletion	delays	PAC clearance during prolonged 37 C stress	`DOI:10.3390/ijms241311202` Results 2.3 and Figure 4c.
HSP104 deletion	delays	Rho1.C17R-GFP turnover during prolonged 37 C stress	`DOI:10.3390/ijms241311202` Results 2.3 and Figure 4d-e; separate protein-level measurement.

Discussions

INTERPRETATION (OPEN): Resolve the operational overlap of PAC with INQ and CytoQ without forcing exact synonymy. The same protein-quality-control literature uses different names and experimental boundaries.
CURATION_TODO (OPEN): Resolve exact family grounding for Btn2-type, Hsp104-type and heterogeneous cargo classes. Domains, broad superfamilies and variable cargo cannot be made exact component identities.
INTERPRETATION (RESOLVED): Keep reporters and upstream or turnover factors separate from demonstrated residents. Genetic effects do not alone demonstrate membership in the assembled structure.
INTERPRETATION (RESOLVED): Preserve temperature, strain, inhibitor and readout boundaries. Reporter foci, protein abundance, refolding and degradation are different measurements.
CURATION_TODO (OPEN): Extend the bounded component list after inspecting the defining paper and supplemental localization data. The curated core is not a complete native PAC inventory.
CURATION_TODO (OPEN): Resolve native client inventories, prevalence and physical properties with structure-specific evidence. Two yeast models and reporter assays do not establish pan-fungal or pan-eukaryotic distribution.

Datasets

Cabrera et al. PAC manuscript dataset, version 2 (DOI:10.17632/z3hvg9wtvg.2) · OTHER · OTHER
Metadata-only link. Native version-2 page gives publication date 2023-03-21, contributor Margarita Cabrera and CC BY 4.0. File manifest and raw archives were not inspected; no file count, sample count, assay inventory or reanalysis finding is asserted.
- https://data.mendeley.com/datasets/z3hvg9wtvg/2 Native version-2 landing page verifies the dataset identity, date, contributor, publication association and licence.

Evidence

GO:0140453 Active cellular-component identity verified through native QuickGO; definition paraphrased, and GO's broad PAC abbreviation scope retained.
GO:0043232 Native QuickGO lists GO:0140453 as an is_a child of intracellular membraneless organelle; no nuclear or cytoplasmic parthood is forced.
DOI:10.3390/ijms241311202 Boronat et al. (2023), PMID 37446379, PMC10342647.1. Native metadata/JATS, all main Results, Discussion, Methods and seven figure captions read. Figure 2 pixels inspected. Supplemental figures/tables and raw data were not independently inspected.
DOI:10.1016/j.celrep.2020.01.077 Cabrera et al. (2020), PMID 32075773. PubMed abstract and bibliographic metadata read. DOI/Cell PDF routes failed and the publisher full-text route returned 403; NCBI reports no PMC copy, not absence of the paper. Detailed mechanistic claims here rely on the readable 2023 study, not an inferred reading of the 2020 full text.

Curation history

2026-10-05T10:53:12Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T10:55:40Z codex · EXPANDED_RECORD — Added bounded GO identity, four component classes, three reference proteins, three intervention graphs, dataset metadata, source-limit discussions and an inspected CC BY 4.0 figure.

Source: data/structures/inclusion/protein_aggregate_center.yaml