Evidence map›Paper›PMID 18678918›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Ion permeation through a Cl--selective channel designed from a CLC Cl-/H+ exchanger.

Hariharan Jayaram, Alessio Accardi, Fang Wu, Carole Williams, Christopher Miller

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
–field-weighted citation impact
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

61 citing papers in PubMed.

  1. A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Membrane Exporters of Fluoride Ion.Annual review of biochemistry · 2021
    Review
  6. Article
  7. Article
  8. Article
  9. Mutation of external glutamate residue reveals a new intermediate transport state and anion binding site in a CLC ClProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  10. Article
  11. A CLC-type FNature structural & molecular biology · 2018
    Article
  12. Article
  13. Article
  14. Multiscale Kinetic Modeling Reveals an Ensemble of ClJournal of the American Chemical Society · 2018
    Article
  15. Chloride Ion Transport by theFrontiers in chemistry · 2018
    Article
  16. Article
  17. Article
  18. Article
  19. A macroscopic H+ and Cl- ions pump via reconstitution of EcClC membrane proteins in lipidic cubic mesophases.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  20. Article

1 more citing papers are in PubMed but not listed here.

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.

Hariharan JayaramDepartment of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
Alessio Accardi
Fang Wu
Carole Williams
Christopher Miller

Funding

Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
NIBIB NIH HHS P30 EB009998
6 · The paper itself

Abstract

The CLC family of Cl(-)-transporting proteins includes both Cl(-) channels and Cl(-)/H(+) exchange transporters. CLC-ec1, a structurally known bacterial homolog of the transporter subclass, exchanges two Cl(-) ions per proton with strict, obligatory stoichiometry. Point mutations at two residues, Glu(148) and Tyr(445), are known to impair H(+) movement while preserving Cl(-) transport. In the x-ray crystal structure of CLC-ec1, these residues form putative "gates" flanking an ion-binding region. In mutants with both of the gate-forming side chains reduced in size, H(+) transport is abolished, and unitary Cl(-) transport rates are greatly increased, well above values expected for transporter mechanisms. Cl(-) transport rates increase as side-chain volume at these positions is decreased. The crystal structure of a doubly ungated mutant shows a narrow conduit traversing the entire protein transmembrane width. These characteristics suggest that Cl(-) flux through uncoupled, ungated CLC-ec1 occurs via a channel-like electrodiffusion mechanism rather than an alternating-exposure conformational cycle that has been rendered proton-independent by the gate mutations.

Indexed as

ProtonsAmino Acid SubstitutionAnimalsChloride ChannelsChloridesCrystallography, X-RayHumansIon TransportPoint MutationProtein Structure, TertiaryChloride ChannelsChloridesProtons

Identifiers

PMID18678918
PMCPMC2516207

What OpenQuestion holds

Textmetadata
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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.