Agonist efficiency links binding and gating in a nicotinic receptor.
acetylcholine
affinity
allostery
dose-response
efficacy
induced fit
molecular biophysics
receptor theory
structural biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
03 07 2023
03 07 2023
Historique:
received:
29
01
2023
accepted:
15
06
2023
medline:
5
7
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
epublish
Résumé
Receptors signal by switching between resting (C) and active (O) shapes ('gating') under the influence of agonists. The receptor's maximum response depends on the difference in agonist binding energy, O minus C. In nicotinic receptors, efficiency (η) represents the fraction of agonist binding energy applied to a local rearrangement (an induced fit) that initiates gating. In this receptor, free energy changes in gating and binding can be interchanged by the conversion factor η. Efficiencies estimated from concentration-response curves (23 agonists, 53 mutations) sort into five discrete classes (%): 0.56 (17), 0.51(32), 0.45(13), 0.41(26), and 0.31(12), implying that there are 5 C versus O binding site structural pairs. Within each class efficacy and affinity are corelated linearly, but multiple classes hide this relationship. η unites agonist binding with receptor gating and calibrates one link in a chain of coupled domain rearrangements that comprises the allosteric transition of the protein.
Identifiants
pubmed: 37399234
doi: 10.7554/eLife.86496
pii: 86496
pmc: PMC10317499
doi:
pii:
Substances chimiques
Receptors, Nicotinic
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS064969
Pays : United States
Organisme : NIH HHS
ID : NS-064969
Pays : United States
Informations de copyright
© 2023, Indurthi and Auerbach.
Déclaration de conflit d'intérêts
DI, AA No competing interests declared
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