Evidence map›Paper›PMID 26878552›Full record

ArticleNature chemical biology2016

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

Sasha S Grimm, Ehud Y Isacoff

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Nonsubstrate PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Voltage sensors.Molecular pharmacology · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. DNA storage-from natural biology to synthetic biology.Computational and structural biotechnology journal · 2023
    Review
  10. Mechanism of voltage gating in the voltage-sensing phosphatase Ci-VSP.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP).Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Article
  13. Article
  14. With PIPs, you get ZIPs and blips.The Journal of general physiology · 2019
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Molecular mechanisms of coupling to voltage sensors in voltage-evoked cellular signals.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Sasha S GrimmBiophysics Graduate Group, University of California, Berkeley, California, USA.
Ehud Y IsacoffBiophysics Graduate Group, University of California, Berkeley, California, USA.
University of California, Berkeley · US

Funding

MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008295 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H, WEMMER, DAVID E · 1989 to 2022
$8.1M
Optical Control of Synaptic Transmission for in Vivo Analysis of Brain Circuits and BehaviorU01NS090527 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD, KRAMER, RICHARD H · 2014 to 2016
$2.4M
Voltage Gating MechanismsR01GM117051 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2016 to 2019
$1.3M
NIGMS NIH HHS R01 GM117051NIGMS NIH HHS R01GM117051NIGMS NIH HHS T32 GM008295NIGMS NIH HHS T32GM008295NINDS NIH HHS U01 NS090527
6 · The paper itself

Abstract

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Indexed as

Allosteric RegulationAllosteric SiteAnimalsCatalytic DomainCiona intestinalisFluorescence Resonance Energy TransferModels, MolecularMutagenesis, Site-DirectedOocytesPatch-Clamp TechniquesPhosphatidylinositolsPhosphoric Monoester HydrolasesSubstrate SpecificityXenopus laevisPhosphatidylinositolsPhosphoric Monoester Hydrolasesvoltage-sensor-containing phosphatase, Ciona intestinalis

Identifiers

PMID26878552
PMCPMC4798927
OpenAlexW2281236506

What OpenQuestion holds

Textmetadata
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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.