Evidence map›Paper›PMID 33028677›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

An intrinsically disordered motif regulates the interaction between the p47 adaptor and the p97 AAA+ ATPase.

Alexander E Conicella, Rui Huang, Zev A Ripstein, Ai Nguyen, Eric Wang, Thomas Löhr, Peter Schuck, Michele Vendruscolo, John L Rubinstein, Lewis E Kay

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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

18 citing papers in PubMed, 35 citations in OpenAlex.

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  7. P-NADs:Heliyon · 2024
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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

10 authors at 3 institutions in 3 countries.

Alexander E ConicellaDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.ORCID 0000-0003-3383-3036
Rui HuangDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; ruihuangchem@gmail.com kay@pound.med.utoronto.ca.ORCID 0000-0002-4064-6397
Zev A RipsteinDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.ORCID 0000-0003-3601-0596
Ai NguyenNational Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Eric WangCentre for Misfolding Diseases, Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom.ORCID 0000-0003-0330-0597
Thomas LöhrCentre for Misfolding Diseases, Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom.ORCID 0000-0003-2969-810X
Peter SchuckNational Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0002-8859-6966
Michele VendruscoloCentre for Misfolding Diseases, Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom.ORCID 0000-0002-3616-1610
John L RubinsteinDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Lewis E KayDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; ruihuangchem@gmail.com kay@pound.med.utoronto.ca.
University of Toronto · CAUniversity of Cambridge · GBNational Institutes of Health · US

Funding

CIHR FDN-503573CIHR PJT-162186
6 · The paper itself

Abstract

VCP/p97, an enzyme critical to proteostasis, is regulated through interactions with protein adaptors targeting it to specific cellular tasks. One such adaptor, p47, forms a complex with p97 to direct lipid membrane remodeling. Here, we use NMR and other biophysical methods to study the structural dynamics of p47 and p47-p97 complexes. Disordered regions in p47 are shown to be critical in directing intra-p47 and p47-p97 interactions via a pair of previously unidentified linear motifs. One of these, an SHP domain, regulates p47 binding to p97 in a manner that depends on the nucleotide state of p97. NMR and electron cryomicroscopy data have been used as restraints in molecular dynamics trajectories to develop structural ensembles for p47-p97 complexes in adenosine diphosphate (ADP)- and adenosine triphosphate (ATP)-bound conformations, highlighting differences in interactions in the two states. Our study establishes the importance of intrinsically disordered regions in p47 for the formation of functional p47-p97 complexes.

Indexed as

Adaptor Proteins, Signal TransducingAdenosine DiphosphateAdenosine TriphosphatasesAdenosine TriphosphateAmino Acid MotifsHumansIntrinsically Disordered ProteinsModels, MolecularNuclear ProteinsProtein BindingProtein ConformationAdaptor Proteins, Signal TransducingAdenosine DiphosphateAdenosine TriphosphatasesAdenosine TriphosphateIntrinsically Disordered ProteinsNuclear Proteinsp37 protein, humanp97 ATPaseintrinsically disorderedmethyl-TROSYp47p97/VCPstructural dynamics

Identifiers

PMID33028677
PMCPMC7585011
OpenAlexW3092499450

What OpenQuestion holds

Textmetadata
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.