Evidence map›Paper›PMID 28757208›Full record

ArticleMolecular cell2017

Vps34 Kinase Domain Dynamics Regulate the Autophagic PI 3-Kinase Complex.

Goran Stjepanovic, Sulochanadevi Baskaran, Mary G Lin, James H Hurley

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Article
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  5. Article
  6. The human autophagy-initiating complexes ULK1C and PI3KC3-C1.The Journal of biological chemistry · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Review
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  16. Review
  17. Cloning and Identification of Common Carp (Current issues in molecular biology · 2024
    Article
  18. Article
  19. Article
  20. Review

12 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Goran StjepanovicDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Sulochanadevi BaskaranDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Mary G LinDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.
James H HurleyDepartment of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jimhurley@berkeley.edu.
QB3 · USLawrence Berkeley National Laboratory · US

Funding

TUBULIN STRUCTURE BY ELECTRON CRYSTALLOGRAPHYP01GM051487 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI CATE, JAMIE H · 1994 to 2018
$27.6M
The Autophagy Initiation ComplexesR01GM111730 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H · 2014 to 2021
$2.2M
NIGMS NIH HHS P01 GM051487NIGMS NIH HHS R01 GM111730
6 · The paper itself

Abstract

The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is required for the initiation of essentially all macroautophagic processes. PI3KC3-C1 consists of the lipid kinase catalytic subunit VPS34, the VPS15 scaffold, and the regulatory BECN1 and ATG14 subunits. The VPS34 catalytic domain and BECN1:ATG14 subcomplex do not touch, and it is unclear how allosteric signals are transmitted to VPS34. We used EM and crosslinking mass spectrometry to dissect five conformational substates of the complex, including one in which the VPS34 catalytic domain is dislodged from the complex but remains tethered by an intrinsically disordered linker. A "leashed" construct prevented dislodging without interfering with the other conformations, blocked enzyme activity in vitro, and blocked autophagy induction in yeast cells. This pinpoints the dislodging and tethering of the VPS34 catalytic domain, and its regulation by VPS15, as a master allosteric switch in autophagy induction.

Indexed as

AutophagyAdaptor Proteins, Vesicular TransportAllosteric RegulationAutophagy-Related ProteinsBeclin-1Class III Phosphatidylinositol 3-KinasesHEK293 CellsHumansMass SpectrometryMutationProtein Interaction Domains and MotifsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionStructure-Activity RelationshipVacuolar Sorting Protein VPS15Adaptor Proteins, Vesicular TransportATG14 protein, humanAutophagy-Related ProteinsBeclin-1Beclin 1 protein, S cerevisiaeBECN1 protein, humanClass III Phosphatidylinositol 3-KinasesPIK3R4 protein, humanSaccharomyces cerevisiae ProteinsVacuolar Sorting Protein VPS15VPS15 protein, S cerevisiaeallosteryautophagycrosslinking mass spectrometryelectron microscopylipid kinasephosphoinositideprotein dynamicsprotein kinaseprotein structurepseudokinase

Identifiers

PMID28757208
PMCPMC5573195
OpenAlexW2738289776

What OpenQuestion holds

Textmetadata
LicenceTDM
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.