insoluble protein deposit

cellstructuremech:insoluble_protein_deposit · Inclusion · Inclusion body · Proposed

A perivacuolar cytoplasmic protein inclusion characterized in budding yeast that accumulates poorly mobile, insoluble protein aggregates, including amyloid and prion cargo, at a site distinct from nuclear and juxtanuclear quality-control deposits. [DOI:10.1038/nature07195]

PrD-GFP recruitment and recovery in yeast Myo2-aid cells. Panels A-D show dispersed foci after depletion and coalescence after auxin washout; E distinguishes persistence of a preformed IPOD from the recruitment defect in F. Microscopy scale bars: 2 micrometers. B, E and F are quantifications, not micrographs. FLUORESCENCE · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Rajesh Kumar, Peter P. Nawroth and Jens Tyedmers (2016), Figure 3; CC BY 4.0, via PubMed Central. Unmodified. · CC_BY_4_0 · source: PMC PMC5045159.1 pgen.1006324.g003 · `DOI:10.1371/journal.pgen.1006324`

Synonyms: IPOD

Part of: GO:0005737 — cytoplasm (no local record)

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
heterogeneous IPOD protein aggregate cargo	Other	part of	Reviewed label only (reviewed name; no accession asserted)			UNKNOWN	Deposited insoluble protein material, including prion and amyloid substrates; no single cargo protein is asserted as an invariant scaffold. `DOI:10.1038/nature07195` Results and Figures 2 and 4 identify perivacuolar deposition of Rnq1, Ure2 and HttQ103 reporters and low mobility of IPOD-localized Ubc9ts. `DOI:10.1371/journal.pgen.1006324` Results use the Sup35 prion-domain reporter PrD-GFP to follow delivery to a central IPOD. This is engineered cargo, not full-length Sup35 membership in every deposit.
Hsp104-type disaggregase	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP104		UNKNOWN	Chaperone associated with assembled IPOD material. In the tested PrD-GFP chase, Hsp104 inhibition prevents slow deposit decay and cargo turnover. This post-assembly intervention does not establish a universal de novo assembly requirement. `DOI:10.1038/nature07195` Figure 5e and Results report Hsp104 enrichment around the IPOD; this is localization, not a fixed coat stoichiometry. `DOI:10.1371/journal.pgen.1006324` Figure 6C-G supports Hsp104-dependent processing in the PrD-GFP chase, using guanidinium inhibition. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P31539/?page_size=200` Complete native integrated match set inspected on 2026-10-05; next=null. Family hits remain broader than the curated component.

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.

Hsp104-type disaggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P31539`	Heat shock protein 104	HSP104	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (3 references) Reviewed reference-sequence example of yeast Hsp104; not a reassignment of 74D-694 experiments to S288C. `UniProtKB:P31539` Native reviewed entry verifies protein name, HSP104/YLL026W and reference taxon 559292. `DOI:10.1038/nature07195` Figure 5e and its Results describe functional GFP-Hsp104 associated with IPOD inclusions. `DOI:10.1371/journal.pgen.1006324` Figure 6C-G tests Hsp104-sensitive persistence and turnover of previously formed PrD-GFP deposits.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — IPOD cargo recruitment and turnover were studied in 74D-694 derivatives carrying PrD-GFP. Methods distinguish galactose-inducible reporter strains from constitutive reporter strains lacking the endogenous SUP35 prion domain. No exact strain taxon is inferred from reference-protein metadata. [DOI:10.1371/journal.pgen.1006324]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence provenance for the reviewed Hsp104 example, not an assertion that the imaged 74D-694 derivatives are S288C. [UniProtKB:P31539]

Functions

spatial sequestration of insoluble protein cargo — Concentrates selected aggregate substrates in a perivacuolar deposit. The entry does not assign universal protection, toxicity or obligatory prion nucleation to every IPOD.
- DOI:10.1038/nature07195 Figures 2 and 4 distinguish amyloid-cargo localization and poorly exchanging IPOD material from the juxtanuclear compartment.
- DOI:10.1371/journal.pgen.1006324 Figures 2, 3 and 5 show reversible defects in accumulation of PrD-GFP at one central IPOD after transport perturbations.
conditional release of sequestered cargo for turnover — In the PrD-GFP chase, deposits can slowly lose cargo through Hsp104-dependent processing, with subsequent turnover partly sensitive to proteasome inhibition. This is not evidence that all IPOD cargo is recoverable or that deposition is an obligatory degradation intermediate.
- DOI:10.1371/journal.pgen.1006324 Figure 6C-G and Results separate slow Hsp104-sensitive deposit decay from downstream, partially MG132-sensitive turnover.

Mechanism graphs

Recruitment of PrD-GFP to a central IPOD (ASSEMBLY)

Subject	Predicate	Object	Evidence
Induced PrD-GFP amyloid cargo	accumulates at	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figures 2A and 2E compare control deposition with depletion conditions.
Myo2 depletion during cargo induction	impairs cargo recruitment to	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figures 2E-F and 3E-F separate recruitment from maintenance.
Tpm1 loss with Tpm2 depletion	impairs cargo recruitment to	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figure 2A-D tests Tpm1/Tpm2 perturbation, auxin controls and viability.
Sec18 depletion during cargo induction	impairs cargo recruitment to	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figure 5B-E tests Sec18 depletion, localization and viability.
Restoration of Myo2 after auxin washout	restores cargo accumulation at	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figure 3A-D includes time-lapse observations of coalescence.
Restoration of Sec18 after auxin washout	restores cargo accumulation at	Insoluble protein deposit	`DOI:10.1371/journal.pgen.1006324` Figure 5B-C includes the auxin-washout rescue.

Hsp104-sensitive processing of deposited PrD-GFP (FUNCTION)

Subject	Predicate	Object	Evidence
PrD-GFP-containing IPOD	can undergo	Gradual liberation of deposited PrD-GFP	`DOI:10.1371/journal.pgen.1006324` Figure 6C-D tracks pre-existing aggregates, accounting for newly budded cells.
Hsp104-type disaggregase	supports	Gradual liberation of deposited PrD-GFP	`DOI:10.1371/journal.pgen.1006324` Figure 6C-F compares slow decay with persistence after Hsp104 inhibition.
Guanidinium treatment during the chase	inhibits	Hsp104-type disaggregase	`DOI:10.1371/journal.pgen.1006324` Figure 6E-G uses 5 mM GdnHCl and reports persistent deposits and reporter protein.
Gradual liberation of deposited PrD-GFP	permits	Turnover of released PrD-GFP	`DOI:10.1371/journal.pgen.1006324` Figure 6G contrasts chase turnover with reporter retention under GdnHCl.
MG132 treatment during the chase	reduces	Turnover of released PrD-GFP	`DOI:10.1371/journal.pgen.1006324` Figure 6G and accompanying Results compare control, MG132 and GdnHCl treatments.

Discussions

INTERPRETATION (RESOLVED): Keep IPOD separate from PAS, INQ/JUNQ and a generic inclusion body. Shared proximity or substrate overlap does not establish exact structure identity.
CURATION_TODO (OPEN): Resolve exact source-neutral component groundings and native cargo inventories. A heterogeneous aggregate class and narrower Hsp104-type class cannot inherit arbitrary broader family identities.
INTERPRETATION (RESOLVED): Distinguish transport machinery and neighboring PAS components from IPOD constituents. Recruitment defects, pulldown association and partial colocalization do not establish stable composition.
INTERPRETATION (RESOLVED): Do not equate IPOD with mandatory autophagic disposal or irreversible sequestration of every cargo. The Ubc9ts recovery assay and the PrD-GFP chase test different substrates and conditions.
INTERPRETATION (RESOLVED): Do not assert obligatory IPOD localization for all prion formation. Perturbation results depend on genotype and stress context.
CURATION_TODO (OPEN): Resolve native assembly scaffolds, broader prevalence and condition-specific material properties. Reporter deposition in one species does not establish a constitutive structure in every lineage or invariant dimensions.

Evidence

DOI:10.1038/nature07195 Original IPOD identity, perivacuolar localization, aggregate mobility and Hsp104 association in yeast.
DOI:10.1371/journal.pgen.1006324 Primary intervention study of cargo recruitment, recovery and slow Hsp104-sensitive processing.
DOI:10.1371/journal.pgen.1011194 Figure 6A limits claims that IPOD localization is obligatory for oxidant-induced prion formation in every genetic background.

Curation history

2026-10-05T07:22:50Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T07:25:34Z codex · EXPANDED_RECORD — Added yeast-scoped IPOD composition, source-bounded recruitment and turnover graphs, interpretation boundaries, reference metadata and an inspected CC BY 4.0 primary figure.

Source: data/structures/inclusion/insoluble_protein_deposit.yaml