Evidence map›Paper›PMID 27710770›Full record

ArticleeLife2016

Atomic mutagenesis in ion channels with engineered stoichiometry.

John D Lueck, Adam L Mackey, Daniel T Infield, Jason D Galpin, Jing Li, Benoît Roux, Christopher A Ahern

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. 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
1.2field-weighted citation impact, top 19% 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, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Pore-modulating toxins exploit inherent slow inactivation to block KProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  13. Article
  14. Article
  15. 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

7 authors at 2 institutions in 1 country.

John D LueckDepartment of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, United States.
Adam L MackeyDepartment of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, United States.
Daniel T InfieldDepartment of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, United States.
Jason D GalpinDepartment of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, United States.
Jing LiDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
Benoît RouxDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.ORCID 0000-0002-5254-2712
Christopher A AhernDepartment of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, United States.ORCID 0000-0002-7975-2744
University of Iowa · USUniversity of Chicago · US

Funding

Synthetic Antigen Binder CoreU54GM087519 · NIGMS · UNIVERSITY OF CHICAGO · PI NAKAMOTO, ROBERT K. · 2010 to 2017
$31.9M
Computational Studies of Ion Channels - Resubmission 01R01GM062342 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI ROUX, BENOIT · 2001 to 2022
$8.7M
Chemical Biology of Voltage-Gated Sodium and Potassium ChannelsR01GM106569 · NIGMS · UNIVERSITY OF IOWA · PI AHERN, CHRISTOPHER A · 2013 to 2022
$2.7M
NIGMS NIH HHS R01 GM062342NIGMS NIH HHS R01 GM106569NIGMS NIH HHS U54 GM087519
6 · The paper itself

Abstract

C-type inactivation of potassium channels fine-tunes the electrical signaling in excitable cells through an internal timing mechanism that is mediated by a hydrogen bond network in the channels' selectively filter. Previously, we used nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole hydrogen bond in Shaker potassium channels with a non-hydrogen bonding homologue of tryptophan, Ind (Pless et al., 2013). Here, molecular dynamics simulations indicate that the Trp434Ind hydrogen bonding partner, Asp447, unexpectedly 'flips out' towards the extracellular environment, allowing water to penetrate the space behind the selectivity filter while simultaneously reducing the local negative electrostatic charge. Additionally, a protein engineering approach is presented whereby split intein sequences are flanked by endoplasmic reticulum retention/retrieval motifs (ERret) are incorporated into the N- or C- termini of Shaker monomers or within sodium channels two-domain fragments. This system enabled stoichiometric control of Shaker monomers and the encoding of multiple amino acids within a channel tetramer.

Indexed as

Amino Acid SequenceAnimalsBinding SitesGene ExpressionHEK293 CellsHumansIon Channel GatingKineticsMembrane PotentialsModels, MolecularMolecular Dynamics SimulationMutagenesis, Site-DirectedMutationNAV1.4 Voltage-Gated Sodium ChannelOocytesPatch-Clamp TechniquesNAV1.4 Voltage-Gated Sodium ChannelRecombinant Fusion ProteinsSCN4A protein, humanShaker Superfamily of Potassium Channelsatomic mutagenesisbiochemistrybiophysicsC-type inactivationintein protein ligationmolecular dynamicsnoncanonical amino acidsstructural biologyvoltage-gated sodium channelsxenopus

Identifiers

PMID27710770
PMCPMC5092047
OpenAlexW2529452645

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.