Principal pathway coupling agonist binding to channel gating in nicotinic receptors

Won Yong Lee, Steven M. Sine

Research output: Contribution to journalArticle

228 Scopus citations

Abstract

Synaptic receptors respond to neurotransmitters by opening an intrinsic ion channel in the final step in synaptic transmission. How binding of the neurotransmitter is conveyed over the long distance to the channel remains a central question in neurobiology. Here we delineate a principal pathway that links neurotransmitter binding to channel gating by using a structural model of the Torpedo acetylcholine receptor at 4-Å resolution, recordings of currents through single receptor channels and determinations of energetic coupling between pairs of residues. We show that a pair of invariant arginine and glutamate residues in each receptor α-subunit electrostatically links peripheral and inner β-sheets from the binding domain and positions them to engage with the channel. The key glutamate and flanking valine residues energetically couple to conserved proline and serine residues emerging from the top of the channel-forming α-helix, suggesting that this is the point at which the binding domain triggers opening of the channel. The series of interresidue couplings identified here constitutes a primary allosteric pathway that links neurotransmitter binding to channel gating.

Original languageEnglish (US)
Pages (from-to)243-247
Number of pages5
JournalNature
Volume438
Issue number7065
DOIs
StatePublished - Nov 10 2005

ASJC Scopus subject areas

  • General

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