title: Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels.
abstract: Molecular determinants of ion channel tetramerization are well characterized, but those involved in heteromeric channel assembly are less clearly understood. The heteromeric composition of native channels is often precisely controlled. Cyclic nucleotide-gated (CNG) channels from rod photoreceptors exhibit a 3:1 stoichiometry of CNGA1 and CNGB1 subunits that tunes the channels for their specialized role in phototransduction. Here we show, using electrophysiology, fluorescence, biochemistry, and X-ray crystallography, that the mechanism for this controlled assembly is the formation of a parallel 3-helix coiled-coil domain of the carboxy-terminal leucine zipper region of CNGA1 subunits, constraining the channel to contain three CNGA1 subunits, followed by preferential incorporation of a single CNGB1 subunit. Deletion of the carboxy-terminal leucine zipper domain relaxed the constraint and permitted multiple CNGB1 subunits in the channel. The X-ray crystal structures of the parallel 3-helix coiled-coil domains of CNGA1 and CNGA3 subunits were similar, suggesting that a similar mechanism controls the stoichiometry of cone CNG channels.
authors: Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, USA.
authors: Noah G
authors: NG
authors: Shuart
authors: Yoni
authors: Y
authors: Haitin
authors: Stacey S
authors: SS
authors: Camp
authors: Kevin D
authors: KD
authors: Black
authors: William N
authors: WN
authors: Zagotta
mesh_terms: D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008968:Molecular Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: C518243:CNGA1 protein, human; C518235:CNGB1 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels