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Structural basis for modulation and agonist specificity of HCN pacemaker channels.

Zagotta WN, Olivier NB, Black KD, Young EC, Olson R, Gouaux E
Nature 425 200-5 (2003)
Related entries: 1q3e, 1q43

Cited: 419 times
EuropePMC logo PMID: 12968185

Abstract

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

Reviews - 1q5o mentioned but not cited (6)

  1. Structural insights into the mechanisms of CNBD channel function. James ZM, Zagotta WN. J Gen Physiol 150 225-244 (2018)
  2. HCN Channels Modulators: The Need for Selectivity. Novella Romanelli M, Sartiani L, Masi A, Mannaioni G, Manetti D, Mugelli A, Cerbai E. Curr Top Med Chem 16 1764-1791 (2016)
  3. HERG potassium channel regulation by the N-terminal eag domain. Gustina AS, Trudeau MC. Cell Signal 24 1592-1598 (2012)
  4. HCN Channels: New Therapeutic Targets for Pain Treatment. Ramírez D, Zúñiga R, Concha G, Zúñiga L. Molecules 23 E2094 (2018)
  5. The EAG Voltage-Dependent K+ Channel Subfamily: Similarities and Differences in Structural Organization and Gating. Barros F, de la Peña P, Domínguez P, Sierra LM, Pardo LA. Front Pharmacol 11 411 (2020)
  6. From Deep Mutational Mapping of Allosteric Protein Landscapes to Deep Learning of Allostery and Hidden Allosteric Sites: Zooming in on "Allosteric Intersection" of Biochemical and Big Data Approaches. Verkhivker G, Alshahrani M, Gupta G, Xiao S, Tao P. Int J Mol Sci 24 7747 (2023)

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Reviews citing this publication (66)

  1. Hyperpolarization-activated cation channels: from genes to function. Biel M, Wahl-Schott C, Michalakis S, Zong X. Physiol Rev 89 847-885 (2009)
  2. hERG K(+) channels: structure, function, and clinical significance. Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. Physiol Rev 92 1393-1478 (2012)
  3. The role of the funny current in pacemaker activity. DiFrancesco D. Circ Res 106 434-446 (2010)
  4. The distribution and targeting of neuronal voltage-gated ion channels. Lai HC, Jan LY. Nat Rev Neurosci 7 548-562 (2006)
  5. CNG and HCN channels: two peas, one pod. Craven KB, Zagotta WN. Annu Rev Physiol 68 375-401 (2006)
  6. The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Yu FH, Catterall WA. Sci STKE 2004 re15 (2004)
  7. Neurophysiology of HCN channels: from cellular functions to multiple regulations. He C, Chen F, Li B, Hu Z. Prog Neurobiol 112 1-23 (2014)
  8. Molecular mechanism of TRP channels. Zheng J. Compr Physiol 3 221-242 (2013)
  9. Physiology and pharmacology of the cardiac pacemaker ("funny") current. Baruscotti M, Bucchi A, Difrancesco D. Pharmacol Ther 107 59-79 (2005)
  10. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Heusch G. Br J Pharmacol 153 1589-1601 (2008)
  11. Capturing cyclic nucleotides in action: snapshots from crystallographic studies. Rehmann H, Wittinghofer A, Bos JL. Nat Rev Mol Cell Biol 8 63-73 (2007)
  12. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Yang F, Zheng J. Protein Cell 8 169-177 (2017)
  13. Exploring HCN channels as novel drug targets. Postea O, Biel M. Nat Rev Drug Discov 10 903-914 (2011)
  14. Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development. Robichaux WG, Cheng X. Physiol Rev 98 919-1053 (2018)
  15. K+ uptake in plant roots. The systems involved, their regulation and parallels in other organisms. Nieves-Cordones M, Alemán F, Martínez V, Rubio F. J Plant Physiol 171 688-695 (2014)
  16. The cardiac pacemaker current. Baruscotti M, Barbuti A, Bucchi A. J Mol Cell Cardiol 48 55-64 (2010)
  17. Signal transducing membrane complexes of photoreceptor outer segments. Wensel TG. Vision Res 48 2052-2061 (2008)
  18. Prokaryotic K(+) channels: from crystal structures to diversity. Kuo MM, Haynes WJ, Loukin SH, Kung C, Saimi Y. FEMS Microbiol Rev 29 961-985 (2005)
  19. The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels. Sartiani L, Mannaioni G, Masi A, Novella Romanelli M, Cerbai E. Pharmacol Rev 69 354-395 (2017)
  20. Properties of shaker-type potassium channels in higher plants. Gambale F, Uozumi N. J Membr Biol 210 1-19 (2006)
  21. Molecular architecture of the vanilloid receptor. Insights for drug design. Ferrer-Montiel A, García-Martínez C, Morenilla-Palao C, García-Sanz N, Fernández-Carvajal A, Fernández-Ballester G, Planells-Cases R. Eur J Biochem 271 1820-1826 (2004)
  22. HCN-related channelopathies. Baruscotti M, Bottelli G, Milanesi R, DiFrancesco JC, DiFrancesco D. Pflugers Arch 460 405-415 (2010)
  23. Cyclic nucleotide-regulated cation channels. Biel M. J Biol Chem 284 9017-9021 (2009)
  24. Monitoring of cAMP synthesis and degradation in living cells. Nikolaev VO, Lohse MJ. Physiology (Bethesda) 21 86-92 (2006)
  25. Function and dysfunction of CNG channels: insights from channelopathies and mouse models. Biel M, Michalakis S. Mol Neurobiol 35 266-277 (2007)
  26. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy. Michalakis S, Becirovic E, Biel M. Int J Mol Sci 19 E749 (2018)
  27. Biophysical techniques for detection of cAMP and cGMP in living cells. Sprenger JU, Nikolaev VO. Int J Mol Sci 14 8025-8046 (2013)
  28. Oxidative modulation of voltage-gated potassium channels. Sahoo N, Hoshi T, Heinemann SH. Antioxid Redox Signal 21 933-952 (2014)
  29. Cooperative and uncooperative cyclic-nucleotide-gated ion channels. Cukkemane A, Seifert R, Kaupp UB. Trends Biochem Sci 36 55-64 (2011)
  30. Factors and pathways involved in capacitation: how are they regulated? Jin SK, Yang WX, Yang WX. Oncotarget 8 3600-3627 (2017)
  31. Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics. Banerjee U, Cheng X. Gene 570 157-167 (2015)
  32. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Hofmann F, Biel M, Kaupp UB. Pharmacol Rev 57 455-462 (2005)
  33. Mechanisms and physiological implications of cooperative gating of clustered ion channels. Dixon RE, Navedo MF, Binder MD, Santana LF. Physiol Rev 102 1159-1210 (2022)
  34. Control of cardiac rate by "funny" channels in health and disease. Barbuti A, DiFrancesco D. Ann N Y Acad Sci 1123 213-223 (2008)
  35. A structural view of ligand-dependent activation in thermoTRP channels. Steinberg X, Lespay-Rebolledo C, Brauchi S. Front Physiol 5 171 (2014)
  36. The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data. Minor DL. Neuron 54 511-533 (2007)
  37. Evolution and Structural Characteristics of Plant Voltage-Gated K+ Channels. Jegla T, Busey G, Assmann SM. Plant Cell 30 2898-2909 (2018)
  38. The enigmatic cytoplasmic regions of KCNH channels. Morais-Cabral JH, Robertson GA. J Mol Biol 427 67-76 (2015)
  39. The fast and slow ups and downs of HCN channel regulation. Lewis AS, Estep CM, Chetkovich DM. Channels (Austin) 4 215-231 (2010)
  40. Phosphatidylinositol 4,5-bisphosphate interactions with the HERG K(+) channel. Bian JS, McDonald TV. Pflugers Arch 455 105-113 (2007)
  41. The structural biology of ryanodine receptors. Kimlicka L, Van Petegem F. Sci China Life Sci 54 712-724 (2011)
  42. The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness. Brown RL, Strassmaier T, Brady JD, Karpen JW. Curr Pharm Des 12 3597-3613 (2006)
  43. Ih from synapses to networks: HCN channel functions and modulation in neurons. Combe CL, Gasparini S. Prog Biophys Mol Biol 166 119-132 (2021)
  44. Getting to the heart of hERG K(+) channel gating. Perry MD, Ng CA, Mann SA, Sadrieh A, Imtiaz M, Hill AP, Vandenberg JI. J Physiol 593 2575-2585 (2015)
  45. Gating in CNGA1 channels. Mazzolini M, Marchesi A, Giorgetti A, Torre V. Pflugers Arch 459 547-555 (2010)
  46. Quickening the pace: looking into the heart of HCN channels. Rosenbaum T, Gordon SE. Neuron 42 193-196 (2004)
  47. Dynamic structural investigations on the torpedo nicotinic acetylcholine receptor by time-resolved photoaffinity labeling. Mourot A, Grutter T, Goeldner M, Kotzyba-Hibert F. Chembiochem 7 570-583 (2006)
  48. Intracellular regions of potassium channels: Kv2.1 and heag. Wray D. Eur Biophys J 38 285-292 (2009)
  49. The domain and conformational organization in potassium voltage-gated ion channels. Pischalnikova AV, Sokolova OS. J Neuroimmune Pharmacol 4 71-82 (2009)
  50. Allosteric modulation of ion channels: the case of maxi-K. Rothberg BS. Sci STKE 2004 pe16 (2004)
  51. Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains. Codding SJ, Johnson AA, Trudeau MC. Channels (Austin) 14 294-309 (2020)
  52. Paradigm shift: new concepts for HCN4 function in cardiac pacemaking. Hennis K, Biel M, Fenske S, Wahl-Schott C. Pflugers Arch 474 649-663 (2022)
  53. Speeding Up the Heart? Traditional and New Perspectives on HCN4 Function. Hennis K, Rötzer RD, Piantoni C, Biel M, Wahl-Schott C, Fenske S. Front Physiol 12 669029 (2021)
  54. Review: HCN Channels in the Heart. Depuydt AS, Peigneur S, Tytgat J. Curr Cardiol Rev 18 e040222200836 (2022)
  55. Noncanonical Ion Channel Behaviour in Pain. Ciotu CI, Tsantoulas C, Meents J, Lampert A, McMahon SB, Ludwig A, Fischer MJM. Int J Mol Sci 20 E4572 (2019)
  56. Patch fluorometry: shedding new light on ion channels. Zheng J. Physiology (Bethesda) 21 6-12 (2006)
  57. Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives. Al Kury LT, Chacar S, Alefishat E, Khraibi AA, Nader M. Front Endocrinol (Lausanne) 13 946313 (2022)
  58. cyclic AMP Regulation and Its Command in the Pacemaker Channel HCN4. Porro A, Thiel G, Moroni A, Saponaro A. Front Physiol 11 771 (2020)
  59. Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies. Gerhardt MJ, Priglinger SG, Biel M, Michalakis S. Biomedicines 11 269 (2023)
  60. The ERG1 K+ Channel and Its Role in Neuronal Health and Disease. Sanchez-Conde FG, Jimenez-Vazquez EN, Auerbach DS, Jones DK. Front Mol Neurosci 15 890368 (2022)
  61. The structure of the apo cAMP-binding domain of HCN4 - a stepping stone toward understanding the cAMP-dependent modulation of the hyperpolarization-activated cyclic-nucleotide-gated ion channels. Akimoto M, VanSchouwen B, Melacini G. FEBS J 285 2182-2192 (2018)
  62. Involvement of the S4-S5 linker and the C-linker domain regions to voltage-gating in plant Shaker channels: comparison with animal HCN and Kv channels. Nieves-Cordones M, Gaillard I. Plant Signal Behav 9 e972892 (2014)
  63. Optical approaches for single-cell and subcellular analysis of GPCR-G protein signaling. Kankanamge D, Ratnayake K, Senarath K, Tennakoon M, Harmon E, Karunarathne A. Anal Bioanal Chem 411 4481-4508 (2019)
  64. Pacemaker Channels and the Chronotropic Response in Health and Disease. Hennis K, Piantoni C, Biel M, Fenske S, Wahl-Schott C. Circ Res 134 1348-1378 (2024)
  65. Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels. Hu Z, Yang J. Channels (Austin) 17 2273165 (2023)
  66. Ivabradine in Patients with Stable Coronary Artery Disease: A Rationale for Use in Addition to and Beyond Percutaneous Coronary Intervention. Godino C, Colombo A, Margonato A. Clin Drug Investig 37 105-120 (2017)

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