The heteromeric cyclic nucleotide gated channel adopts a 3A : 1B stoichiometry

Article

关键词: ROD PHOTORECEPTOR;    ION CHANNELS;    BETA-SUBUNIT;    C-ELEGANS;    SENSITIVITY;    ARRANGEMENT;    NEURONS;    FAMILY;    CAMP;   

DOI  :  10.1038/nature01201

来源: SCIE

【 摘 要 】

Cyclic nucleotide-gated (CNG) channels are crucial for visual and olfactory transductions(1-4). These channels are tetramers and in their native forms are composed of A and B subunits(5), with a stoichiometry thought to be 2A:2B (refs 6, 7). Here we report the identification of a leucine-zipper(8)-homology domain named CLZ (for carboxy-terminal leucine zipper). This domain is present in the distal C terminus of CNG channel A subunits but is absent from B subunits, and mediates an inter-subunit interaction. With cross-linking, non-denaturing gel electrophoresis and analytical centrifugation, this CLZ domain was found to mediate a trimeric interaction. In addition, a mutant cone CNG channel A subunit with its CLZ domain replaced by a generic trimeric leucine zipper produced channels that behaved much like the wild type, but less so if replaced by a dimeric or tetrameric leucine zipper. This A-subunit-only, trimeric interaction suggests that heteromeric CNG channels actually adopt a 3A:1B stoichiometry. Biochemical analysis of the purified bovine rod CNG channel confirmed this conclusion. This revised stoichiometry provides a new foundation for understanding the structure and function of the CNG channel family.

【 授权许可】

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