Structure and Rearrangements in the Carboxy-Terminal Region ofSpIH Channels
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.
- Research Organization:
- COLLABORATION - Howard Hughes MedicalInstitute/U. Washington
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 910337
- Report Number(s):
- LBNL-63058; TRN: US200724%%2
- Journal Information:
- Structure, Vol. 15; Related Information: Journal Publication Date: 06/2007
- Country of Publication:
- United States
- Language:
- English
Similar Records
Dual expression of constitutively active Gαs-protein-coupled receptors differentially establishes the resting activity of the cAMP-gated HCN2 channel in a single compartment
Effects of pH on allosteric and catalytic properties of the guanosine cyclic 3',5'-phosphate stimulated cyclic nucleotide phosphodiesterase from calf liver