Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Structure
2007 Jun 01;156:671-82. doi: 10.1016/j.str.2007.04.008.
Show Gene links
Show Anatomy links
Structure and rearrangements in the carboxy-terminal region of SpIH channels.
Flynn GE
,
Black KD
,
Islas LD
,
Sankaran B
,
Zagotta WN
.
???displayArticle.abstract???
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels regulate the spontaneous firing activity and electrical excitability of many cardiac and neuronal cells. The modulation of HCN channel opening by the direct binding of cAMP underlies many physiological processes such as the autonomic regulation of the heart rate. Here we use a combination of X-ray crystallography and electrophysiology to study the allosteric mechanism for cAMP modulation of HCN channels. SpIH is an invertebrate HCN channel that is activated fully by cAMP, but only partially by cGMP. We exploited the partial agonist action of cGMP on SpIH to reveal the molecular mechanism for cGMP specificity of many cyclic nucleotide-regulated enzymes. Our results also elaborate a mechanism for the allosteric conformational change in the cyclic nucleotide-binding domain and a mechanism for partial agonist action. These mechanisms will likely extend to other cyclic nucleotide-regulated channels and enzymes as well.
Adams,
Recent developments in the PHENIX software for automated crystallographic structure determination.
2004, Pubmed
Adams,
Recent developments in the PHENIX software for automated crystallographic structure determination.
2004,
Pubmed
Altenhofen,
Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium.
1991,
Pubmed
,
Xenbase
Altomare,
Integrated allosteric model of voltage gating of HCN channels.
2001,
Pubmed
Baruscotti,
Pacemaker channels.
2004,
Pubmed
Biel,
Cardiac HCN channels: structure, function, and modulation.
2002,
Pubmed
Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed
Clayton,
Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
2004,
Pubmed
Collaborative Computational Project, Number 4,
The CCP4 suite: programs for protein crystallography.
1994,
Pubmed
Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed
Craven,
Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels.
2004,
Pubmed
,
Xenbase
Davis,
MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes.
2004,
Pubmed
DEL CASTILLO,
Interaction at end-plate receptors between different choline derivatives.
1957,
Pubmed
DiFrancesco,
Muscarinic modulation of cardiac rate at low acetylcholine concentrations.
1989,
Pubmed
DiFrancesco,
The contribution of the 'pacemaker' current (if) to generation of spontaneous activity in rabbit sino-atrial node myocytes.
1991,
Pubmed
Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed
Frisch,
Thermodynamics of the interaction of barnase and barstar: changes in free energy versus changes in enthalpy on mutation.
1997,
Pubmed
Gauss,
Molecular identification of a hyperpolarization-activated channel in sea urchin sperm.
1998,
Pubmed
Gordon,
Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels.
1995,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Heinemann,
Nonstationary noise analysis and application to patch clamp recordings.
1992,
Pubmed
Jones,
Electron-density map interpretation.
1997,
Pubmed
Kaupp,
Molecular diversity of pacemaker ion channels.
2001,
Pubmed
Kumar,
Molecular model of the cyclic GMP-binding domain of the cyclic GMP-gated ion channel.
1992,
Pubmed
Lee,
Mutagenesis of the cyclic AMP receptor protein of Escherichia coli: targeting positions 83, 127 and 128 of the cyclic nucleotide binding pocket.
1994,
Pubmed
Li,
Cyclic nucleotide-gated channels: structural basis of ligand efficacy and allosteric modulation.
1997,
Pubmed
Mayer,
Structure and function of glutamate receptor ion channels.
2004,
Pubmed
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
Pape,
Queer current and pacemaker: the hyperpolarization-activated cation current in neurons.
1996,
Pubmed
Rehmann,
Structure and regulation of the cAMP-binding domains of Epac2.
2003,
Pubmed
Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed
Scott,
Predicted ligand interactions of 3'5'-cyclic nucleotide-gated channel binding sites: comparison of retina and olfactory binding site models.
1996,
Pubmed
Shin,
Inactivation in HCN channels results from reclosure of the activation gate: desensitization to voltage.
2004,
Pubmed
Su,
Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.
1995,
Pubmed
Varnum,
Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels.
1995,
Pubmed
Vaughan,
A structural double-mutant cycle: estimating the strength of a buried salt bridge in barnase.
2002,
Pubmed
Vigil,
A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.
2006,
Pubmed
Weber,
Crystal structure of a cyclic AMP-independent mutant of catabolite gene activator protein.
1987,
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
Zagotta,
Gating of single Shaker potassium channels in Drosophila muscle and in Xenopus oocytes injected with Shaker mRNA.
1989,
Pubmed
,
Xenbase
Zagotta,
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
2003,
Pubmed
