@article {10108,
	title = {Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	number = {40},
	year = {2014},
	note = {<p>Saponaro, AndreaPauleta, Sofia RCantini, FrancescaMatzapetakis, ManolisHammann, ChristianDonadoni, ChiaraHu, LeiThiel, GerhardBanci, LuciaSantoro, BinaMoroni, AnnaR01 NS036658/NS/NINDS NIH HHS/United StatesR56 NS036658/NS/NINDS NIH HHS/United StatesNS36658/NS/NINDS NIH HHS/United StatesResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tUnited StatesProceedings of the National Academy of Sciences of the United States of AmericaProc Natl Acad Sci U S A. 2014 Oct 7;111(40):14577-82. doi: 10.1073/pnas.1410389111. Epub 2014 Sep 2.</p>
},
	month = {Oct 07},
	pages = {14577-82},
	edition = {2014/09/10},
	abstract = {<p>cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by interacting with the channel CNBD. To unravel the molecular mechanisms underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free form and mapped on it the TRIP8b interaction site. We reconstruct here the full conformational changes induced by cAMP binding to the HCN channel CNBD. Our results show that TRIP8b does not compete with cAMP for the same binding region; rather, it exerts its inhibitory action through an allosteric mechanism, preventing the cAMP-induced conformational changes in the HCN channel CNBD.</p>
},
	keywords = {*Ion Channel Gating, Binding Sites, Channels/*chemistry/metabolism, Crystallography, X-Ray, Cyclic AMP/*chemistry/metabolism, Cyclic Nucleotide-Gated Cation Channels/chemistry/metabolism, Electrophoresis, Polyacrylamide Gel, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Potassium Channels/chemistry/metabolism, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear/*chemistry/metabolism},
	isbn = {1091-6490 (Electronic)0027-8424 (Linking)},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25197093},
	author = {Saponaro, A. and Pauleta, S. R. and Cantini, F. and Matzapetakis, M. and Hammann, C. and Donadoni, C. and Hu, L. and Thiel, G. and Banci, L. and Santoro, B. and Moroni, A.}
}
