Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin

Maria E. Grunwald, Haining Zhong, Jun Lai, King Wai Yau

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The action of calmodulin (CAM) on target proteins is important for a variety of cellular functions. We demonstrate here, however, that the presence of a CaM-binding site on a protein does not necessarily imply a functional effect. The α-subunit of the cGMP-gated cation channel of human retinal cones has a CaM-binding site on its cytoplasmic N-terminal region, but the homomeric channel that it forms is not functionally modulated by CaM. Mutational analysis based on comparison to the highly homologous olfactory cyclic nucleotide-gated channel α-subunit, which does form a CaM-modulated channel, indicates that residues downstream of the CaM-binding domain on these channels are also important for CaM to have an effect. These findings suggest that a CaM-binding site and complementary structural features in a protein probably evolve independently, and an effect caused by CaM occurs only in the presence of both elements. More generally, the same may be true for other recognized binding sites on proteins for modulators or activators, so that a demonstrated physical interaction does not necessarily imply functional consequence.

Original languageEnglish (US)
Pages (from-to)13444-13449
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number23
DOIs
StatePublished - Nov 9 1999
Externally publishedYes

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Cyclic Nucleotides
Calmodulin
Binding Sites
Proteins
Cyclic Nucleotide-Gated Cation Channels
Retinal Cone Photoreceptor Cells
Cations

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin. / Grunwald, Maria E.; Zhong, Haining; Lai, Jun; Yau, King Wai.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 23, 09.11.1999, p. 13444-13449.

Research output: Contribution to journalArticle

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