Evidence map›Paper›PMID 41876484›Full record

ArticleNature communications2026

Substrate-interacting pore loops of two ATPase subunits determine the degradation efficiency of the 26S proteasome.

Erika López-Alfonzo, Ayush Saurabh, Sahar Zarafshan, Connor Arkinson, Christine L Gee, Hao-Hsuan Hsieh, Steve Pressé, Andreas Martin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

8 authors.

Erika López-AlfonzoDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA.
Ayush SaurabhDepartment of Physics, Center for Biological Physics, Arizona State University, Tempe, AZ, USA.ORCID http://orcid.org/0000-0001-8482-782X
Sahar ZarafshanDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA.
Connor ArkinsonDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-3665-2484
Christine L GeeDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2632-6418
Hao-Hsuan HsiehDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA.
Steve PresséDepartment of Physics, Center for Biological Physics, Arizona State University, Tempe, AZ, USA.ORCID http://orcid.org/0000-0002-5408-0718
Andreas MartinDepartment of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA. a.martin@berkeley.edu.ORCID http://orcid.org/0000-0003-0923-3284

Funding

ATP-Dependent Protein Unfolding and Translocation by the Eukaryotic ProteasomeR01GM094497 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MARTIN, ANDREAS · 2011 to 2024
$3.7M
NIGMS NIH HHS R01 GM094497U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01-GM094497
6 · The paper itself

Abstract

The 26S proteasome is the major eukaryotic protease responsible for the degradation of misfolded, damaged, and obsolete regulatory proteins. Commitment to degradation occurs when conserved pore loops in the heterohexameric ATPase motor of the proteasome engage the flexible initiation region of a polyubiquitinated protein substrate for subsequent mechanical unfolding and translocation into a proteolytic chamber. Here, we use in vitro biochemical assays, single-molecule FRET-based measurements, and cryo-EM structure determination to characterize how the pore-1 loops of individual ATPase subunits in the yeast 26S proteasome contribute to the different steps of substrate degradation and affect the proteasome conformational dynamics. We find that the pore-1 loops of the Rpt6 and Rpt4 ATPase subunits play particularly important, yet distinct roles in substrate capture and unfolding, and in holding the ATPase motor in a static state prior to substrate engagement. Interestingly, these pore-1 loop contributions correlate with the positions of ATPase subunits in spiral-staircase arrangements for the substrate-free and substrate-degrading proteasome, providing insights into the mechanisms of substrate processing by the 26S proteasome and related ATPase motors.

Indexed as

Adenosine TriphosphatasesProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCryoelectron MicroscopyFluorescence Resonance Energy TransferModels, MolecularProtein ConformationProtein SubunitsProteolysisAdenosine TriphosphatasesATP dependent 26S proteaseProteasome Endopeptidase ComplexProtein SubunitsRPT6 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID41876484
PMCPMC13186983

What OpenQuestion holds

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Registered trials

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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.