Evidence map›Paper›PMID 25267652›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Conformational cycle and ion-coupling mechanism of the Na+/hydantoin transporter Mhp1.

Kelli Kazmier, Shruti Sharma, Shahidul M Islam, Benoît Roux, Hassane S Mchaourab

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
12.9field-weighted citation impact, top 1% 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

50 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Integrated AlphaFold2 and DEER investigation of the conformational dynamics of a pH-dependent APC antiporter.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021
    Review
  15. Article
  16. Article
  17. Unconventional transport of metal ions and protons by Nramps.The Journal of general physiology · 2019
    Article
  18. The allosteric mechanism of substrate-specific transport in SLC6 is mediated by a volumetric sensor.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  19. Article
  20. 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

5 authors at 2 institutions in 1 country.

Kelli KazmierChemical and Physical Biology Program, Vanderbilt University, Nashville, TN 37230; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232; and.
Shruti SharmaDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232; and.
Shahidul M IslamDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637.
Benoît RouxDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637.
Hassane S MchaourabChemical and Physical Biology Program, Vanderbilt University, Nashville, TN 37230; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232; and hassane.mchaourab@vanderbilt.edu.
Vanderbilt University · USUniversity of Chicago · US

Funding

Synthetic Antigen Binder CoreU54GM087519 · NIGMS · UNIVERSITY OF CHICAGO · PI JAVITCH, JONATHAN A · 2010 to 2017
$31.9M
Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Pulsed Q-band EPR SpectrometerS10RR027091 · NCRR · VANDERBILT UNIVERSITY · PI BETH, ALBERT H · 2010 to 2010
$483k
Conformational Changes Underlying Intracellular Gating of the Leucine TransporterF31MH095383 · NIMH · VANDERBILT UNIVERSITY · PI KAZMIER, KELLI · 2011 to 2012
$55k
NCATS NIH HHS UL1 TR000430NCRR NIH HHS S10 RR027091NCRR NIH HHS S10RR027091NIGMS NIH HHS U54 GM087519NIGMS NIH HHS U54-GM087519NIMH NIH HHS F31 MH095383NIMH NIH HHS F31-MH095383-01
6 · The paper itself

Abstract

Ion-dependent transporters of the LeuT-fold couple the uptake of physiologically essential molecules to transmembrane ion gradients. Defined by a conserved 5-helix inverted repeat that encodes common principles of ion and substrate binding, the LeuT-fold has been captured in outward-facing, occluded, and inward-facing conformations. However, fundamental questions relating to the structural basis of alternating access and coupling to ion gradients remain unanswered. Here, we used distance measurements between pairs of spin labels to define the conformational cycle of the Na(+)-coupled hydantoin symporter Mhp1 from Microbacterium liquefaciens. Our results reveal that the inward-facing and outward-facing Mhp1 crystal structures represent sampled intermediate states in solution. Here, we provide a mechanistic context for these structures, mapping them into a model of transport based on ion- and substrate-dependent conformational equilibria. In contrast to the Na(+)/leucine transporter LeuT, our results suggest that Na(+) binding at the conserved second Na(+) binding site does not change the energetics of the inward- and outward-facing conformations of Mhp1. Comparative analysis of ligand-dependent alternating access in LeuT and Mhp1 lead us to propose that different coupling schemes to ion gradients may define distinct conformational mechanisms within the LeuT-fold class.

Indexed as

ActinomycetalesBacterial ProteinsCrystallography, X-RayExtracellular SpaceHydantoinsIonsIon TransportLigandsModels, MolecularProtein ConformationSodiumSubstrate SpecificityBacterial ProteinsHydantoinsIonsLigandsSodiumconformational dynamicsDEEREPRNa+-coupled symporttransport mechanism

Identifiers

PMID25267652
PMCPMC4205665
OpenAlexW2046394498

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.