Evidence map›Paper›PMID 30028291›Full record

ArticleeLife2018

Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures.

Jan Rheinberger, Xiaolong Gao, Philipp Am Schmidpeter, Crina M Nimigean

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

42 citing papers in PubMed, 61 citations in OpenAlex.

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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 1 institution in 1 country.

Jan RheinbergerDepartments of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0002-9901-2065
Xiaolong GaoDepartments of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0001-8933-9286
Philipp Am SchmidpeterDepartments of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0003-2871-9706
Crina M NimigeanDepartments of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0002-6254-4447
Cornell University · US

Funding

TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
Molecular Mechanisms of Potassium Channel Permeation and GatingR01GM088352 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI NIMIGEAN, CRINA M · 2010 to 2025
$5.6M
Structural dynamics in cyclic nucleotide-modulated channelsR01GM124451 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI NIMIGEAN, CRINA M · 2017 to 2024
$3.2M
NIGMS NIH HHS P41 GM103310NIGMS NIH HHS R01 GM088352NIGMS NIH HHS R01GM088352NIGMS NIH HHS R01 GM124451NIGMS NIH HHS R01GM124451NIGMS NIH HHS R01GM124451 and R01GM088352
6 · The paper itself

Abstract

Cyclic nucleotide-modulated channels have important roles in visual signal transduction and pacemaking. Binding of cyclic nucleotides (cAMP/cGMP) elicits diverse functional responses in different channels within the family despite their high sequence and structure homology. The molecular mechanisms responsible for ligand discrimination and gating are unknown due to lack of correspondence between structural information and functional states. Using single particle cryo-electron microscopy and single-channel recording, we assigned functional states to high-resolution structures of SthK, a prokaryotic cyclic nucleotide-gated channel. The structures for apo, cAMP-bound, and cGMP-bound SthK in lipid nanodiscs, correspond to no, moderate, and low single-channel activity, respectively, consistent with the observation that all structures are in resting, closed states. The similarity between apo and ligand-bound structures indicates that ligand-binding domains are strongly coupled to pore and SthK gates in an allosteric, concerted fashion. The different orientations of cAMP and cGMP in the 'resting' and 'activated' structures suggest a mechanism for ligand discrimination.

Indexed as

Cryoelectron MicroscopyCyclic AMPCyclic GMPCyclic Nucleotide-Gated Cation ChannelsModels, MolecularProtein BindingProtein ConformationSpirochaetaCyclic AMPCyclic GMPCyclic Nucleotide-Gated Cation Channelsallosterycryo-electron microscopycyclic nucleotide-gated ion channelE. colilipid nanodiscmolecular biophysicspartial agonismsingle-channel recordingstructural biology

Identifiers

PMID30028291
PMCPMC6093708
OpenAlexW2883690729

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.