Dynamics of the acetylcholine receptor pore at the gating transition state

Ananya Mitra, Gisela D. Cymes, Anthony Auerbach

Research output: Contribution to journalArticle

Abstract

Neuromuscular acetylcholine receptors (AChRs) are ion channels that alternatively adopt stable conformations that either allow (open) or prohibit (closed) ionic conduction. We probed the dynamics of pore (M2) residues at the diliganded gating transition state by using single-channel kinetic and rate-equilibrium free energy relationship (Φ-value) analyses of mutant AChRs. The mutations were at the equatorial (9′) position of the α, β, and ε subunits (n = 15) or at sites between the equator and the extracellular domain in the α-subunit (n = 8), We also studied AChRs having only one of the two α-subunits mutated. The results indicate that the α-subunit, like the δ-subunit, has a region of flexure near the middle of M2, that the two α-subunits experience distinct energy barriers to gating at the equator (but not else-where), and that the collective subunit motions at the equator are asymmetric during the AChR gating isomerization.

Original languageEnglish (US)
Pages (from-to)15069-15074
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number42
DOIs
StatePublished - Oct 18 2005

Keywords

  • Ion channels
  • Phi-value
  • Rate-equilibrium free energy relationship (REFER) analysis

ASJC Scopus subject areas

  • General

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