The heteromeric cyclic nucleotide-gated channel adopts a 3A

1B stoichlometry

Haining Zhong, Laurie L. Molday, Robert S. Molday, King Wai Yau

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Cyclic nucleotide-gated (CNG) channels are crucial for visual and olfactory transductions1-4. These channels are tetramers and in their native forms are composed of A and B subunits5, with a stoichiometry thought to be 2A:2B (refs 6, 7). Here we report the identification of a leucine-zipper8-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.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalNature
Volume420
Issue number6912
DOIs
StatePublished - Nov 14 2002
Externally publishedYes

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Cyclic Nucleotide-Gated Cation Channels
Leucine Zippers
Centrifugation
Leucine
Electrophoresis
Gels

ASJC Scopus subject areas

  • General

Cite this

The heteromeric cyclic nucleotide-gated channel adopts a 3A : 1B stoichlometry. / Zhong, Haining; Molday, Laurie L.; Molday, Robert S.; Yau, King Wai.

In: Nature, Vol. 420, No. 6912, 14.11.2002, p. 193-198.

Research output: Contribution to journalArticle

Zhong, Haining ; Molday, Laurie L. ; Molday, Robert S. ; Yau, King Wai. / The heteromeric cyclic nucleotide-gated channel adopts a 3A : 1B stoichlometry. In: Nature. 2002 ; Vol. 420, No. 6912. pp. 193-198.
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