title: Calmodulin controls the rod photoreceptor CNG channel through an unconventional binding site in the N-terminus of the beta-subunit.
abstract: Calmodulin (CaM) controls the activity of the rod cGMP-gated ion channel by decreasing the apparent cGMP affinity. We have examined the mechanism of this modulation using electrophysiological and biochemical techniques. Heteromeric channels, consisting of alpha- and beta-subunits, display a high CaM sensitivity (EC50 </=5 nM) similar to the native channel. Using surface plasmon resonance spectroscopy, we identified two unconventional CaM-binding sites (CaM1 and CaM2), one in each of the N- and the C-terminal regions of the beta-subunit. Ca2+ co-operatively stimulates binding of CaM to these sites exactly within the range of [Ca2+] occurring during a light response. Deletion of the N-terminal CaM1 site results in channels that are no longer CaM-sensitive, whereas deletion of CaM2 has only minor effects. We discuss different models to explain the high-affinity binding of CaM.
authors.affiliation: Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, D-52425 Jülich.
authors.forename: D
authors.initials: D
authors.lastname: Weitz
authors.forename: M
authors.initials: M
authors.lastname: Zoche
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: H G
authors.initials: HG
authors.lastname: Körschen
authors.forename: U B
authors.initials: UB
authors.lastname: Kaupp
authors.forename: K W
authors.initials: KW
authors.lastname: Koch
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010786:Photoreceptor Cells / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins; D007473:Ion Channels; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I