Evidence mapPaperPMID 35614850Full record

ArticleBiophysical journal2022

Proton coupling and the multiscale kinetic mechanism of a peptide transporter.

Chenghan Li, Zhi Yue, Simon Newstead, Gregory A Voth

Open access · greenAbstract read
In one paragraph

Article in Biophysical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026
    Article
  2. pH-Driven βACS omega · 2026
    Article
  3. Article
  4. Conformational Landscape of the Di- and Tripeptide Permease A Transport Cycle.Journal of chemical information and modeling · 2025
    Article
  5. Article
  6. Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Article
  9. CHARMM-GUIJournal of chemical theory and computation · 2023
    Review
  10. Article
  11. Review
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 2 countries.

Chenghan LiDepartment of Chemistry, Chicago Center for Theoretical Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois.
Zhi YueDepartment of Chemistry, Chicago Center for Theoretical Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois.
Simon NewsteadDepartment of Biochemistry, University of Oxford, Oxford, UK. Electronic address: simon.newstead@bioch.ox.ac.uk.
Gregory A VothDepartment of Chemistry, Chicago Center for Theoretical Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois. Electronic address: gavoth@uchicago.edu.
Chicago Institute for Psychoanalysis · USUniversity of Oxford · GB

Funding

SIMULATIONS OF PROTON TRANSLOCATION IN BIOMOLECULESR01GM053148 · NIGMS · UNIVERSITY OF UTAH · PI VOTH, GREGORY A. · 1996 to 2021
$5.3M
NIGMS NIH HHS R01 GM053148
6 · The paper itself

Abstract

Proton-coupled peptide transporters (POTs) are crucial for the uptake of di- and tripeptides as well as drug and prodrug molecules in prokaryotes and eukaryotic cells. We illustrate from multiscale modeling how transmembrane proton flux couples within a POT protein to drive essential steps of the full functional cycle: 1) protonation of a glutamate on transmembrane helix 7 (TM7) opens the extracellular gate, allowing ligand entry; 2) inward proton flow induces the cytosolic release of ligand by varying the protonation state of a second conserved glutamate on TM10; 3) proton movement between TM7 and TM10 is thermodynamically driven and kinetically permissible via water proton shuttling without the participation of ligand. Our results, for the first time, give direct computational confirmation for the alternating access model of POTs, and point to a quantitative multiscale kinetic picture of the functioning protein mechanism.

Indexed as

Membrane Transport ProteinsProtonsGlutamic AcidLigandsPeptidesGlutamic AcidLigandsMembrane Transport Proteinspeptide permeasePeptidesProtons

Identifiers

PMID35614850
PMCPMC9279349
OpenAlexW4281482245

What Socratic 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 Socratic graph.