Evidence map›Paper›PMID 24655503›Full record

ArticleBiophysical journal2014

Structural determinants of water permeation through the sodium-galactose transporter vSGLT.

Joshua L Adelman, Ying Sheng, Seungho Choe, Jeff Abramson, Ernest M Wright, John M Rosenberg, Michael Grabe

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Interactions of Arachidonic Acid with AAC1 and UCP1.International journal of molecular sciences · 2025
    Article
  2. Article
  3. Review
  4. Article
  5. Collective Domain Motion Facilitates Water Transport in SGLT1.International journal of molecular sciences · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Novel and Unexpected Functions of SGLTs.Physiology (Bethesda, Md.) · 2017
    Review
  13. Review
  14. Structural and functional significance of water permeation through cotransporters.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  15. Stochastic steps in secondary active sugar transport.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Joshua L AdelmanDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ying ShengDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Seungho ChoeSchool of Basic Science, College of Convergence, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Korea.
Jeff AbramsonDepartment of Physiology, University of California, Los Angeles, California.
Ernest M WrightDepartment of Physiology, University of California, Los Angeles, California.
John M RosenbergDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: jmr@pitt.edu.
Michael GrabeDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Cardiovascular Research Institute, Department of Pharmaceutical Chemistry, University of California, San Francisco, California. Electronic address: michael.grabe@ucsf.edu.
University of Pittsburgh · USUniversity of California, Los Angeles · USDaegu Gyeongbuk Institute of Science and Technology · KRUniversity of California, San Francisco · US

Funding

TrainingP41GM103712 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FAEDER, JAMES · 2012 to 2021
$16.3M
Structures of sodium glucose transporters by cryo electron microscopyR01GM078844 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABRAMSON, JEFFREY S · 2006 to 2018
$5.3M
MOLECULAR MECHANISMS OF INTESTINAL TRANSPORTR01DK019567 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WRIGHT, ERNEST M · 1986 to 2013
$4.3M
Renal and Epithelial Biology Training ProgramT32DK061296 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2002 to 2022
$3.1M
Computational Studies of Sodium SymportersR01GM089740 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRABE, MICHAEL · 2011 to 2020
$2.8M
NIDDK NIH HHS DK19567NIDDK NIH HHS R01 DK019567NIDDK NIH HHS T32 DK061296NIDDK NIH HHS T32-DK061296NIGMS NIH HHS GM078844NIGMS NIH HHS GM089740-01A1NIGMS NIH HHS P41 GM103712NIGMS NIH HHS P41GM103712-S1NIGMS NIH HHS R01 GM078844NIGMS NIH HHS R01 GM089740
6 · The paper itself

Abstract

Sodium-glucose transporters (SGLTs) facilitate the movement of water across the cell membrane, playing a central role in cellular homeostasis. Here, we present a detailed analysis of the mechanism of water permeation through the inward-facing state of vSGLT based on nearly 10 μs of molecular dynamics simulations. These simulations reveal the transient formation of a continuous water channel through the transporter that permits water to permeate the protein. Trajectories in which spontaneous release of galactose is observed, as well as those in which galactose remains in the binding site, show that the permeation rate, although modulated by substrate occupancy, is not tightly coupled to substrate release. Using a, to our knowledge, novel channel-detection algorithm, we identify the key residues that control water flow through the transporter and show that solvent gating is regulated by side-chain motions in a small number of residues on the extracellular face. A sequence alignment reveals the presence of two insertion sites in mammalian SGLTs that flank these outer-gate residues. We hypothesize that the absence of these sites in vSGLT may account for the high water permeability values for vSGLT determined via simulation compared to the lower experimental estimates for mammalian SGLT1.

Indexed as

Molecular Dynamics SimulationAlgorithmsAmino Acid SequenceAnimalsBinding SitesGalactoseHumansMolecular Sequence DataSodium-Glucose Transport ProteinsGalactoseSodium-Glucose Transport Proteins

Identifiers

PMID24655503
PMCPMC3984995
OpenAlexW2148517939

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.