ArticleBiophysical journal2014
Catch-and-hold activation of muscle acetylcholine receptors having transmitter binding site mutations.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Article
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- Efficiency measures the conversion of agonist binding energy into receptor conformational change.The Journal of general physiology · 2019Article
- A single molecular distance predicts agonist binding energy in nicotinic receptors.The Journal of general physiology · 2019Article
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Cyclic activation of endplate acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structure and dynamics underlying elementary ligand binding events in human pacemaking channels.eLife · 2016Article
- Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.Nature structural & molecular biology · 2016Review
- Structural correlates of affinity in fetal versus adult endplate nicotinic receptors.Nature communications · 2016Article
- Dose-Response Analysis When There Is a Correlation between Affinity and Efficacy.Molecular pharmacology · 2016Article
- Modal affinities of endplate acetylcholine receptors caused by loop C mutations.The Journal of general physiology · 2015Article
- Activation of endplate nicotinic acetylcholine receptors by agonists.Biochemical pharmacology · 2015Review
- Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity.British journal of pharmacology · 2015Article
- Correlating structural and energetic changes in glycine receptor activation.The Journal of biological chemistry · 2015Article
- Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Don't flip out: AChRs are primed to catch and hold your attention.Biophysical journal · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Agonists turn on receptors because their target sites have a higher affinity in the active versus resting conformation of the protein. We used single-channel electrophysiology to measure the lower-affinity (LA) and higher-affinity (HA) equilibrium dissociation constants for acetylcholine in adult-type muscle mouse nicotinic receptors (AChRs) having mutations of agonist binding site amino acids. For a series of agonists and for all mutations of αY93, αG147, αW149, αY190, αY198, εW55, and δW57, the change in LA binding energy was approximately half that in HA binding energy. The results were analyzed as a linear free energy relationship between LA and HA agonist binding, the slope of which (κ) gives the fraction of the overall binding chemical potential where the LA complex is established. The linear correlation between LA and HA binding energies suggests that the overall binding process is by an integrated mechanism (catch-and-hold). For the agonist and the above mutations, κ ∼ 0.5, but side-chain substitutions of two residues had a slope that was significantly higher (0.90; αG153) or lower (0.25; εP121). The results suggest that backbone rearrangements in loop B, loop C, and the non-α surface participate in both LA binding and the LA ↔ HA affinity switch. It appears that all of the intermediate steps in AChR activation comprise a single, energetically coupled process.
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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.