title: Conformational dynamics of the alphaM3 transmembrane helix during acetylcholine receptor channel gating.
abstract: Muscle acetylcholine receptors are synaptic ion channels that "gate" between closed- and open-channel conformations. We used Phi-value analysis to probe the transition state of the diliganded gating reaction with regard to residues in the M3, membrane-spanning helix of the muscle acetylcholine receptor alpha-subunit. Phi (a fraction between 1 and 0) parameterizes the extent to which a mutation changes the opening versus the closing rate constant and, for a linear reaction mechanism, the higher the Phi-value, the "earlier" the gating motion. In the upper half of alphaM3 the gating motions of all five tested residues were temporally correlated (Phi approximately 0.30) and serve to link structural changes occurring at the middle of the M2, pore-lining helix with those occurring at the interface of the extracellular and transmembrane domains. alphaM3 belongs to a complex and diverse set of synchronously moving parts that change structure relatively late in the channel-opening process. The propagation of the gating Brownian conformational cascade has a complex spatial distribution in the transmembrane domain.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cadugan
authors.forename: Anthony
authors.initials: A
authors.lastname: Auerbach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D043587:Receptor, Muscarinic M3 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014101:Torpedo
chemical_list: D010446:Peptide Fragments; D043587:Receptor, Muscarinic M3; D011994:Recombinant Proteins