Evidence map›Paper›PMID 37292947›Full record

ArticlebioRxiv : the preprint server for biology2023

The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions.

Julian R Braxton, Chad R Altobelli, Maxwell R Tucker, Eric Tse, Aye C Thwin, Michelle R Arkin, Daniel R Southworth

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Julian R BraxtonGraduate Program in Chemistry and Chemical Biology; University of California, San Francisco; San Francisco, CA 94158, USA.
Chad R AltobelliGraduate Program in Chemistry and Chemical Biology; University of California, San Francisco; San Francisco, CA 94158, USA.
Maxwell R TuckerDepartment of Biochemistry and Biophysics and Institute for Neurodegenerative Diseases; University of California, San Francisco; San Francisco, CA 94158, USA.
Eric TseDepartment of Biochemistry and Biophysics and Institute for Neurodegenerative Diseases; University of California, San Francisco; San Francisco, CA 94158, USA.
Aye C ThwinDepartment of Biochemistry and Biophysics and Institute for Neurodegenerative Diseases; University of California, San Francisco; San Francisco, CA 94158, USA.
Michelle R ArkinDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center; University of California, San Francisco; San Francisco, CA 94158, USA.
Daniel R SouthworthDepartment of Biochemistry and Biophysics and Institute for Neurodegenerative Diseases; University of California, San Francisco; San Francisco, CA 94158, USA.
University of California, San Francisco · US

Funding

STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Mechanisms of Protein Disaggregation and Turnover by AAA+ ChaperonesR01GM138690 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SOUTHWORTH, DANIEL RYLAND · 2021 to 2024
$1.9M
Protein and small-molecule tools to probe the conformational dependence of the VCP/p97 protein-protein interaction network--Equipment SupplementR01GM130145 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ARKIN, MICHELLE · 2018 to 2021
$1.6M
Structure and function of mitochondrial Hsp60F31GM142279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BRAXTON, JULIAN · 2021 to 2023
$90k
NIGMS NIH HHS F31 GM142279NIGMS NIH HHS R01 GM130145NIGMS NIH HHS R01 GM138690NIGMS NIH HHS T32 GM008284
6 · The paper itself

Abstract

p97/VCP is an essential cytosolic AAA+ ATPase hexamer that extracts and unfolds substrate polypeptides during protein homeostasis and degradation. Distinct sets of p97 adapters guide cellular functions but their roles in direct control of the hexamer are unclear. The UBXD1 adapter localizes with p97 in critical mitochondria and lysosome clearance pathways and contains multiple p97-interacting domains. We identify UBXD1 as a potent p97 ATPase inhibitor and report structures of intact p97:UBXD1 complexes that reveal extensive UBXD1 contacts across p97 and an asymmetric remodeling of the hexamer. Conserved VIM, UBX, and PUB domains tether adjacent protomers while a connecting strand forms an N-terminal domain lariat with a helix wedged at the interprotomer interface. An additional VIM-connecting helix binds along the second AAA+ domain. Together these contacts split the hexamer into a ring-open conformation. Structures, mutagenesis, and comparisons to other adapters further reveal how adapters containing conserved p97-remodeling motifs regulate p97 ATPase activity and structure.

Identifiers

PMID37292947
PMCPMC10245715
OpenAlexW4376646906

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.