ArticleThe Journal of general physiology2003
The role of loop 5 in acetylcholine receptor channel gating.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- High-resolution structures of multiple 5-HTeLife · 2020Article
- Modulation of theeLife · 2020Article
- Molecular recognition at cholinergic synapses: acetylcholine versus choline.The Journal of physiology · 2017Article
- Structural basis for allosteric coupling at the membrane-protein interface in Gloeobacter violaceus ligand-gated ion channel (GLIC).The Journal of biological chemistry · 2014Article
- The energy and work of a ligand-gated ion channel.Journal of molecular biology · 2013Review
- Function of interfacial prolines at the transmitter-binding sites of the neuromuscular acetylcholine receptor.The Journal of biological chemistry · 2013Article
- Energy for wild-type acetylcholine receptor channel gating from different choline derivatives.Biophysical journal · 2013Article
- End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease.Physiological reviews · 2012Review
- Synaptic neurotransmitter-gated receptors.Cold Spring Harbor perspectives in biology · 2012Review
- Structural link between γ-aminobutyric acid type A (GABAA) receptor agonist binding site and inner β-sheet governs channel activation and allosteric drug modulation.The Journal of biological chemistry · 2012Article
- Design and control of acetylcholine receptor conformational change.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Glycine hinges with opposing actions at the acetylcholine receptor-channel transmitter binding site.Molecular pharmacology · 2011Article
- Temperature dependence of acetylcholine receptor channels activated by different agonists.Biophysical journal · 2011Article
- Subunit symmetry at the extracellular domain-transmembrane domain interface in acetylcholine receptor channel gating.The Journal of biological chemistry · 2010Article
- Linking the acetylcholine receptor-channel agonist-binding sites with the gate.Biophysical journal · 2010Article
- Acetylcholine receptor channels activated by a single agonist molecule.Biophysical journal · 2010Article
- Energetics of gating at the apo-acetylcholine receptor transmitter binding site.The Journal of general physiology · 2010Article
- Aromatic Residues {epsilon}Trp-55 and {delta}Trp-57 and the Activation of Acetylcholine Receptor Channels.The Journal of biological chemistry · 2009Article
- Probing protein packing surrounding the residues in and flanking the nicotinic acetylcholine receptor M2M3 loop.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Unliganded gating of acetylcholine receptor channels.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinic acetylcholine receptor channel (AChR) gating is an organized sequence of molecular motions that couples a change in the affinity for ligands at the two transmitter binding sites with a change in the ionic conductance of the pore. Loop 5 (L5) is a nine-residue segment (mouse alpha-subunit 92-100) that links the beta4 and beta5 strands of the extracellular domain and that (in the alpha-subunit) contains binding segment A. Based on the structure of the acetylcholine binding protein, we speculate that in AChRs L5 projects from the transmitter binding site toward the membrane along a subunit interface. We used single-channel kinetics to quantify the effects of mutations to alphaD97 and other L5 residues with respect to agonist binding (to both open and closed AChRs), channel gating (for both unliganded and fully-liganded AChRs), and desensitization. Most alphaD97 mutations increase gating (up to 168-fold) but have little or no effect on ligand binding or desensitization. Rate-equilibrium free energy relationship analysis indicates that alphaD97 moves early in the gating reaction, in synchrony with the movement of the transmitter binding site (Phi = 0.93, which implies an open-like character at the transition state). alphaD97 mutations in the two alpha-subunits have unequal energetic consequences for gating, but their contributions are independent. We conclude that the key, underlying functional consequence of alphaD97 perturbations is to increase the unliganded gating equilibrium constant. L5 emerges as an important and early link in the AChR gating reaction which, in the absence of agonist, serves to increase the relative stability of the closed conformation of the protein.
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Registered trials
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.