Evidence map›Paper›PMID 36279472›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Mechanism of voltage gating in the voltage-sensing phosphatase Ci-VSP.

Rong Shen, Yilin Meng, Benoît Roux, Eduardo Perozo

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Multistate Kinetic Model of the Sodium-Potassium ATPase.The journal of physical chemistry. B · 2025
    Article
  3. Article
  4. Voltage sensors.Molecular pharmacology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Fifty years of gating currents and channel gating.The Journal of general physiology · 2023
    Review
  13. Review
  14. Article
  15. 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
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 1 institution in 1 country.

Rong ShenDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.ORCID 0000-0003-4332-4518
Yilin MengDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.
Benoît RouxDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.ORCID 0000-0002-5254-2712
Eduardo PerozoDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637.ORCID 0000-0001-7132-2793
University of Chicago · US

Funding

Computational Studies of Ion Channels - Resubmission 01R01GM062342 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI ROUX, BENOIT · 2001 to 2022
$8.7M
HIGH RESOLUTION STRUCTURAL DYNAMICS OF K CHANNELSR01GM057846 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI PEROZO, EDUARDO A · 1998 to 2018
$7.4M
Molecular dynamics studies of K+ and Na+ channels and biomembranes based on a polarizable force fieldR35GM152124 · NIGMS · UNIVERSITY OF CHICAGO · PI BENOIT ROUX · 2024 to 2026
$2.2M
Beagle-3: A Shared GPU Cluster for Biomolecular SciencesS10OD028655 · OD · UNIVERSITY OF CHICAGO · PI ROUX, BENOIT · 2020 to 2020
$2.0M
NIGMS NIH HHS R01 GM057846NIGMS NIH HHS R01 GM062342NIGMS NIH HHS R35 GM152124NIH HHS S10 OD028655
6 · The paper itself

Abstract

Conformational changes in voltage-sensing domains (VSDs) are driven by the transmembrane electric field acting on the protein charges. Yet, the overall energetics and detailed mechanism of this process are not fully understood. Here, we determined free energy and displacement charge landscapes as well as the major conformations visited during a complete functional gating cycle in the isolated VSD of the phosphatase Ci-VSP (Ci-VSD) comprising four transmembrane helices (segments S1 to S4). Molecular dynamics simulations highlight the extent of S4 movements. In addition to the crystallographically determined activated "Up" and resting "Down" states, the simulations predict two Ci-VSD conformations: a deeper resting state ("down-minus") and an extended activated ("up-plus") state. These additional conformations were experimentally probed via systematic cysteine mutagenesis with metal-ion bridges and the engineering of proton conducting mutants at hyperpolarizing voltages. The present results show that these four states are visited sequentially in a stepwise manner during voltage activation, each step translocating one arginine or the equivalent of ∼1

Indexed as

Ion Channel GatingProtonsArginineCysteinePhosphoric Monoester HydrolasesProtein Structure, SecondaryArginineCysteinePhosphoric Monoester HydrolasesProtonsCi-VSPenergy landscapegating currentsvoltage dependence

Identifiers

PMID36279472
PMCPMC9636939
OpenAlexW4307188282

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.