title: Molecular rearrangements in the ligand-binding domain of cyclic nucleotide-gated channels.
abstract: Cyclic nucleotide-gated (CNG) channels are activated in response to the direct binding of cyclic nucleotides to an intracellular domain. This domain is thought to contain a beta roll and two alpha helices, designated the B and C helices. To probe the conformational changes occurring in the ligand-binding domain during channel activation, we used the substituted cysteine accessibility method (SCAM). We found that a residue in the beta roll, C505, is more accessible in unliganded channels than in liganded channels, whereas a residue in the C helix, G597C, is more accessible in closed channels than in open channels. These results support a molecular mechanism for channel activation in which the ligand initially binds to the beta roll, followed by an opening allosteric transition involving the relative movement of the C helix toward the beta roll.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle 98105, USA.
authors.forename: K
authors.initials: K
authors.lastname: Matulef
authors.forename: G E
authors.initials: GE
authors.lastname: Flynn
authors.forename: W N
authors.initials: WN
authors.lastname: Zagotta
mesh_terms: D000495:Allosteric Site; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D003545:Cysteine / Q000235:genetics / Q000502:physiology; D005260:Female; D015321:Gene Rearrangement; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D009865:Oocytes; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014982:Xenopus laevis
chemical_list: D007473:Ion Channels; D008024:Ligands; D009712:Nucleotides, Cyclic; D003545:Cysteine