Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels
- Univ. of Washington, Seattle, WA (United States). School of Medicine. Howard Hughes Medical Inst. Dept. of Physiology and Biophysics; DOE/OSTI
- Univ. of Washington, Seattle, WA (United States). School of Medicine. Howard Hughes Medical Inst. Dept. of Physiology and Biophysics
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.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1623877
- Journal Information:
- Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 2; ISSN 2041-1723
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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