title: Dissecting intersubunit contacts in cyclic nucleotide-gated ion channels.
abstract: In cyclic nucleotide-gated (CNG) ion channels, binding of cGMP or cAMP drives a conformational change that leads to opening of an ion-conducting pore. One region implicated in the coupling of ligand binding to opening of the pore is the C linker region. Here, we used crosslinking of endogenous cysteines to study interregion proximity. We demonstrate that an individual amino acid--C481--in the C linker region of each of two neighboring subunits can form a disulfide bond. Further, using tandem dimers, we show that a disulfide bond between C35 in the N-terminal region and C481 in the C linker region can form either within a subunit or between subunits. From our data on proximity between individual amino acids and previous studies, a picture emerges of the C linker as a potential dimerization interface.
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Rosenbaum
authors.forename: Sharona E
authors.initials: SE
authors.lastname: Gordon
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010618:Phenanthrolines / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D014982:Xenopus laevis / Q000502:physiology
chemical_list: D004220:Disulfides; D007473:Ion Channels; D010618:Phenanthrolines; D021122:Protein Subunits; D006152:Cyclic GMP; D003545:Cysteine