biostudies-literatureShuart NGNEI NIH HHSNCRR NIH HHS457https://www.ebi.ac.uk/biostudies/studies/S-EPMC3265371biostudies-literatureUnknown2Molecular 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 singlNature communicationsMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels.PMC3265371S10 RR023748R01 EY010329Black KDShuart NGHaitin YCamp SSZagotta WNfalseMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels.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 singl2011-01-01T00:00:00Z2011 Aug2026-04-30T19:55:36.425Z2019-03-27T00:48:22ZS-EPMC32653712187891110.1038/ncomms1466