Evidence map›Paper›PMID 15504901›Full record

ArticleThe Journal of general physiology2004

Invariant aspartic Acid in muscle nicotinic receptor contributes selectively to the kinetics of agonist binding.

Won Yong Lee, Steven M Sine

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

24 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  3. Review
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  10. Review
  11. Synaptic neurotransmitter-gated receptors.Cold Spring Harbor perspectives in biology · 2012
    Review
  12. Article
  13. Article
  14. Disruption of an intersubunit electrostatic bond is a critical step in glycine receptor activation.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
  15. The positive allosteric modulator morantel binds at noncanonical subunit interfaces of neuronal nicotinic acetylcholine receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009
    Article
  16. Article
  17. Binding to gating transduction in nicotinic receptors: Cys-loop energetically couples to pre-M1 and M2-M3 regions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009
    Article
  18. Article
  19. Article
  20. Structural answers and persistent questions about how nicotinic receptors work.Frontiers in bioscience : a journal and virtual library · 2008
    Review
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

2 authors at 1 institution in 1 country.

Won Yong LeeDepartment of Physiology and Biophysics, Mayo Clinic College of Medicine, 200 First St., SW, MSB 1-35, Rochester, MN 55905, USA.
Steven M Sine
Mayo Clinic in Arizona · US

Funding

STRUCTURE/FUNCTION OF THE ACETYLCHOLINE RECEPTORR01NS031744 · NINDS · MAYO CLINIC ROCHESTER · PI SINE, STEVEN M · 1992 to 2023
$7.3M
Structure and Function of the Acetylcholine ReceptorR37NS031744 · NINDS · MAYO CLINIC ROCHESTER · PI SINE, STEVEN M · 2001 to 2007
$4.1M
NINDS NIH HHS NS31744NINDS NIH HHS R01 NS031744NINDS NIH HHS R37 NS031744
6 · The paper itself

Abstract

We examined functional contributions of interdomain contacts within the nicotinic receptor ligand binding site using single channel kinetic analyses, site-directed mutagenesis, and a homology model of the major extracellular region. At the principal face of the binding site, the invariant alphaD89 forms a highly conserved interdomain contact near alphaT148, alphaW149, and alphaT150. Patch-clamp recordings show that the mutation alphaD89N markedly slows acetylcholine (ACh) binding to receptors in the resting closed state, but does not affect rates of channel opening and closing. Neither alphaT148L, alphaT150A, nor mutations at both positions substantially affects the kinetics of receptor activation, showing that hydroxyl side chains at these positions are not hydrogen bond donors for the strong acceptor alphaD89. However substituting a negative charge at alphaT148, but not at alphaT150, counteracts the effect of alphaD89N, demonstrating that a negative charge in the region of interdomain contact confers rapid association of ACh. Interpreted within the structural framework of ACh binding protein and a homology model of the receptor ligand binding site, these results implicate main chain amide groups in the domain harboring alphaW149 as principal hydrogen bond donors for alphaD89. The specific effect of alphaD89N on ACh association suggests that interdomain hydrogen bonding positions alphaW149 for optimal interaction with ACh.

Indexed as

AcetylcholineAmino Acid SequenceAspartic AcidBinding SitesCell LineHumansKidneyKineticsLigandsMembrane PotentialsMolecular Sequence DataMuscle, SkeletalProtein BindingProtein Structure, TertiaryReceptors, NicotinicRecombinant ProteinsAcetylcholineAspartic AcidLigandsReceptors, NicotinicRecombinant Proteins

Identifiers

PMID15504901
PMCPMC2234004
OpenAlexW2006305915

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.