Evidence map›Paper›PMID 42282567›Full record

ArticlebioRxiv : the preprint server for biology2026

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31.

Frank Adolf, Ellen A Goodall, Ekampreet Singh, Susanne von Gronau, Erignacio Fermin Perez, Darlene Fung, Benedikt Müller, Joao A Paulo, John Hanna, J Wade Harper and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Frank AdolfDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.ORCID 0000-0002-9812-5711
Ellen A GoodallAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0001-9876-5973
Ekampreet SinghDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.ORCID 0000-0002-7976-1608
Susanne von GronauDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Erignacio Fermin PerezDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0009-0008-5022-8886
Darlene FungDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0009-0000-2484-0694
Benedikt MüllerDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.ORCID 0000-0001-5030-2910
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4291-413X
John HannaDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0003-2964-1058
J Wade HarperAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0002-6944-7236
Brenda A SchulmanDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.ORCID 0000-0002-3083-1126

Funding

Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
Regulation of PINK1 and PARKIN-Dependent MitophagyR01NS083524 · NINDS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W · 2020 to 2024
$2.2M
Structural and Functional Analysis of Proteasome Core Particle BiogenesisR01GM144367 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI HANNA, JOHN W · 2022 to 2025
$1.6M
Developing proteomics pipelines to improve depth, throughput, and accuracyR35GM156406 · NIGMS · HARVARD MEDICAL SCHOOL · PI Joao A Paulo · 2025 to 2026
$878k
NIA NIH HHS R01 AG011085NIGMS NIH HHS R01 GM144367NIGMS NIH HHS R35 GM156406NINDS NIH HHS R01 NS083524
6 · The paper itself

Abstract

FBXO7 and PI31 variants are linked to rare Parkinsonian syndromes, implicating their dysfunction in neurodegeneration. We define how both engage each other and regulate the proteasome 20S core particle (CP). In cells, each can associate independently with the proteasome, with multiple domains in FBXO7 contributing. Utilizing cryo-EM we visualized how FBXO7's C-terminal domain engages multiple subunits within the CP interior, blocking the β5 peptidase activity. In contrast, we visualized PI31 engagement of all three catalytic sites within the 20S CP, revealing the previously unknown structural basis for β1 inhibition. Furthermore, we establish how disease-associated variants impact both FBXO7 and PI31 function, including disruption of proteasome inhibition and SKP1-FBXO7-PI31 complex assembly. These results establish an unexpected function for FBXO7, providing a mechanistic basis for investigation of its role in proteasome regulation in Parkinson's disease.

Indexed as

20S core particleCUL1FBXO7PARK15Parkinsonian-Pyramidal syndromeParkinson’s diseasePDPI31PPSproteasome inhibitionproteasomesPSMF1SCF

Identifiers

PMID42282567
PMCPMC13252361

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.