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Proc Natl Acad Sci U S A
1991 Nov 01;8821:9868-72.
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Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium.
Altenhofen W
,
Ludwig J
,
Eismann E
,
Kraus W
,
Bönigk W
,
Kaupp UB
.
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Cyclic nucleotide-gated ionic channels in photoreceptors and olfactory sensory neurons are activated by binding of cGMP or cAMP to a receptor site on the channel polypeptide. By site-directed mutagenesis and functional expression of bovine wild-type and mutant channels in Xenopus oocytes, we have tested the hypothesis that an alanine/threonine difference in the cyclic nucleotide-binding site determines the specificity of ligand binding, as has been proposed for cyclic nucleotide-dependent protein kinases [Weber, I.T., Shabb, J.B. & Corbin, J.D. (1989) Biochemistry 28, 6122-6127]. The wild-type olfactory channel is approximately 25-fold more sensitive to both cAMP and cGMP than the wild-type rod photoreceptor channel, and both channels are 30- to 40-fold more sensitive to cGMP than to cAMP. Substitution of the respective threonine by alanine in the rod photoreceptor and olfactory channels decreases the cGMP sensitivity of channel activation 30-fold but little affects activation by cAMP. Substitution of threonine by serine, an amino acid that also carries a hydroxyl group, even improves cGMP sensitivity of the wild-type channels 2- to 5-fold. We conclude that the hydroxyl group of Thr-560 (rod) and Thr-537 (olfactory) forms an additional hydrogen bond with cGMP, but not cAMP, and thereby provides the structural basis for ligand discrimination in cyclic nucleotide-gated channels.
Baker,
Hydrogen bonding in globular proteins.
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Baker,
Hydrogen bonding in globular proteins.
1984,
Pubmed
Breer,
Rapid kinetics of second messenger formation in olfactory transduction.
1990,
Pubmed
Chau,
Kinetic studies on the dissociation of adenosine cyclic 3',5'-monophosphate from the regulatory subunit of protein kinase from rabbit skeletal muscle.
1980,
Pubmed
Cook,
Identification, purification, and functional reconstitution of the cyclic GMP-dependent channel from rod photoreceptors.
1987,
Pubmed
Delgado,
A cyclic AMP-activated K+ channel in Drosophila larval muscle is persistently activated in dunce.
1991,
Pubmed
Dhallan,
Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons.
1990,
Pubmed
DiFrancesco,
Direct activation of cardiac pacemaker channels by intracellular cyclic AMP.
1991,
Pubmed
Fesenko,
Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.
,
Pubmed
Garges,
Sites of allosteric shift in the structure of the cyclic AMP receptor protein.
1985,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Haynes,
Cyclic GMP-sensitive conductance in outer segment membrane of catfish cones.
,
Pubmed
Hemsley,
A simple method for site-directed mutagenesis using the polymerase chain reaction.
1989,
Pubmed
Kaupp,
The cyclic nucleotide-gated channels of vertebrate photoreceptors and olfactory epithelium.
1991,
Pubmed
Kaupp,
Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
1989,
Pubmed
,
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Konarska,
Recognition of cap structure in splicing in vitro of mRNA precursors.
1984,
Pubmed
Kozak,
Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs.
1984,
Pubmed
Landgraf,
The amino terminus regulates binding to and activation of cGMP-dependent protein kinase.
1989,
Pubmed
Ludwig,
Primary structure of cAMP-gated channel from bovine olfactory epithelium.
1990,
Pubmed
McKay,
Structure of catabolite gene activator protein at 2.9-A resolution. Incorporation of amino acid sequence and interactions with cyclic AMP.
1982,
Pubmed
Melton,
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
1984,
Pubmed
Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase
Nakamura,
A cyclic nucleotide-gated conductance in olfactory receptor cilia.
,
Pubmed
Saiki,
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
1988,
Pubmed
Shabb,
One amino acid change produces a high affinity cGMP-binding site in cAMP-dependent protein kinase.
1990,
Pubmed
Shirley,
Olfactory adenylate cyclase of the rat. Stimulation by odorants and inhibition by Ca2+.
1986,
Pubmed
Stühmer,
Patch clamp characterization of sodium channels expressed from rat brain cDNA.
1987,
Pubmed
,
Xenbase
Tanaka,
Photoreceptor channel activation by nucleotide derivatives.
1989,
Pubmed
Taylor,
cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes.
1990,
Pubmed
Weber,
Predicted structures of the cGMP binding domains of the cGMP-dependent protein kinase: a key alanine/threonine difference in evolutionary divergence of cAMP and cGMP binding sites.
1989,
Pubmed
Weber,
Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
1987,
Pubmed
Yau,
Cyclic GMP-activated conductance of retinal photoreceptor cells.
1989,
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