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PDBsum entry 1q3e

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protein ligands Protein-protein interface(s) links
Transport protein PDB id
1q3e
Jmol
Contents
Protein chains
192 a.a. *
Ligands
PCG ×2
Waters ×330
* Residue conservation analysis
PDB id:
1q3e
Name: Transport protein
Title: Hcn2j 443-645 in the presence of cgmp
Structure: Potassium/sodium hyperpolarization-activated cycl nucleotide-gated channel 2. Chain: a, b. Fragment: residues 443-645 (reference sequence numbering). Synonym: brain cyclic nucleotide gated channel 2, bcng-2, hyperpolarization-activated cation channel 1, hac-1. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organ: brain. Gene: hcn2 or bcng2 or hac1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Octamer (from PDB file)
Resolution:
1.90Å     R-factor:   0.210     R-free:   0.239
Authors: W.N.Zagotta,N.B.Olivier,K.D.Black,E.C.Young,R.Olson,J.E.Goua
Key ref:
W.N.Zagotta et al. (2003). Structural basis for modulation and agonist specificity of HCN pacemaker channels. Nature, 425, 200-205. PubMed id: 12968185 DOI: 10.1038/nature01922
Date:
29-Jul-03     Release date:   09-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O88703  (HCN2_MOUSE) -  Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Seq:
Struc:
 
Seq:
Struc:
863 a.a.
192 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/nature01922 Nature 425:200-205 (2003)
PubMed id: 12968185  
 
 
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
W.N.Zagotta, N.B.Olivier, K.D.Black, E.C.Young, R.Olson, E.Gouaux.
 
  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.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Structure of the mouse HCN2 C-linker and CNBD construct bound to cAMP. a, Ribbon representation of a single protomer of HCN2J with cAMP. b, HCN2 tetramer viewed perpendicular (left) and parallel (right) to the four-fold axis. Each subunit is shown in a different colour. c, Molecular surface representation of the tetramer, coloured according to the calculated electrostatic potential and viewed parallel to the four-fold axis from the intracellular side of the membrane (right). Residues Glu 451, Asp 487, Asp 489 and Asp 609 protrude toward the central axis of the tetramer. The view on the left is perpendicular to the four-fold axis, and the molecule has been sliced along the symmetry axis.
Figure 4.
Figure 4: C-linker interactions and cyclic nucleotide-dependent tetramer formation. a, Stereoview of intersubunit C-linker contacts. Helices A' and B' of one protomer are in red, and helices C' and D' of an adjacent protomer are in blue. b, HCN2I sedimentation equilibrium data in the absence (top) and presence (bottom) of cAMP. The measurements and the models used to fit the experimental data are shown as open yellow circles and thin black lines, respectively. The thick black, red and blue lines represent, respectively, the proportion of monomer, dimer and tetramer calculated from the models. The residuals are shown for a monomer -dimer (red) or a monomer -dimer -tetramer (blue) model (top), and for a monomer -dimer (red) or a monomer -tetramer (blue) model (bottom). c, Cartoon of an unliganded closed channel (left) and a liganded open channel (right).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 425, 200-205) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22230959 T.I.Brelidze, A.E.Carlson, B.Sankaran, and W.N.Zagotta (2012).
Structure of the carboxy-terminal region of a KCNH channel.
  Nature, 481, 530-533.
PDB codes: 3ukn 3ukt 3ukv
20729090 A.Cukkemane, R.Seifert, and U.B.Kaupp (2011).
Cooperative and uncooperative cyclic-nucleotide-gated ion channels.
  Trends Biochem Sci, 36, 55-64.  
  21357734 A.S.Gustina, and M.C.Trudeau (2011).
hERG potassium channel gating is mediated by N- and C-terminal region interactions.
  J Gen Physiol, 137, 315-325.  
21187420 N.L.Wicks, T.Wong, J.Sun, Z.Madden, and E.C.Young (2011).
Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating.
  Proc Natl Acad Sci U S A, 108, 609-614.  
22094868 O.Postea, and M.Biel (2011).
Exploring HCN channels as novel drug targets.
  Nat Rev Drug Discov, 10, 903-914.  
21430265 S.Schünke, M.Stoldt, J.Lecher, U.B.Kaupp, and D.Willbold (2011).
Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel.
  Proc Natl Acad Sci U S A, 108, 6121-6126.
PDB code: 2kxl
21347269 V.Hammelmann, X.Zong, F.Hofmann, S.Michalakis, and M.Biel (2011).
The cGMP-Dependent Protein Kinase II Is an Inhibitory Modulator of the Hyperpolarization-Activated HCN2 Channel.
  PLoS One, 6, e17078.  
20806410 A.Battefeld, C.Bierwirth, Y.C.Li, L.Barthel, T.Velmans, and U.Strauss (2010).
I(h) "run-up" in rat neocortical neurons and transiently rat or human HCN1-expressing HEK293 cells.
  J Neurosci Res, 88, 3067-3078.  
20088482 A.V.Matveev, J.B.Fitzgerald, J.Xu, A.P.Malykhina, K.K.Rodgers, and X.Q.Ding (2010).
The disease-causing mutations in the carboxyl terminus of the cone cyclic nucleotide-gated channel CNGA3 subunit alter the local secondary structure and interfere with the channel active conformational change.
  Biochemistry, 49, 1628-1639.  
20529121 G.W.Wilson, and J.Garthwaite (2010).
Hyperpolarization-activated ion channels as targets for nitric oxide signalling in deep cerebellar nuclei.
  Eur J Neurosci, 31, 1935-1945.  
  20713549 H.P.Larsson (2010).
How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle.
  J Gen Physiol, 136, 237-241.  
21070946 J.Rinaldi, J.Wu, J.Yang, C.Y.Ralston, B.Sankaran, S.Moreno, and S.S.Taylor (2010).
Structure of yeast regulatory subunit: a glimpse into the evolution of PKA signaling.
  Structure, 18, 1471-1482.
PDB code: 3of1
20620873 J.Yang, G.Krishnamoorthy, A.Saxena, G.Zhang, J.Shi, H.Yang, K.Delaloye, D.Sept, and J.Cui (2010).
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.
  Neuron, 66, 871-883.  
20378667 K.Chin, W.Moeder, H.Abdel-Hamid, D.Shahinas, D.Gupta, and K.Yoshioka (2010).
Importance of the alphaC-helix in the cyclic nucleotide binding domain for the stable channel regulation and function of cyclic nucleotide gated ion channels in Arabidopsis.
  J Exp Bot, 61, 2383-2393.  
20213494 M.Baruscotti, G.Bottelli, R.Milanesi, J.C.DiFrancesco, and D.DiFrancesco (2010).
HCN-related channelopathies.
  Pflugers Arch, 460, 405-415.  
19898862 M.Mazzolini, A.Marchesi, A.Giorgetti, and V.Torre (2010).
Gating in CNGA1 channels.
  Pflugers Arch, 459, 547-555.  
  20824064 T.I.Brelidze, A.E.Carlson, D.R.Davies, L.J.Stewart, and W.N.Zagotta (2010).
Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen.
  PLoS One, 5, 0.  
20512974 T.J.Sjoberg, A.P.Kornev, and S.S.Taylor (2010).
Dissecting the cAMP-inducible allosteric switch in protein kinase A RIalpha.
  Protein Sci, 19, 1213-1221.
PDB code: 3iia
  20456426 Y.H.Zhou, L.H.Sun, Z.H.Liu, G.Bu, X.P.Pang, S.C.Sun, G.F.Qiao, B.Y.Li, and J.H.Schild (2010).
Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat.
  Clin Exp Pharmacol Physiol, 37, 852-861.  
19524546 A.O.Rozario, H.K.Turbendian, K.J.Fogle, N.B.Olivier, and G.R.Tibbs (2009).
Voltage-dependent opening of HCN channels: Facilitation or inhibition by the phytoestrogen, genistein, is determined by the activation status of the cyclic nucleotide gating ring.
  Biochim Biophys Acta, 1788, 1939-1949.  
19132361 A.V.Nair, C.Anselmi, and M.Mazzolini (2009).
Movements of native C505 during channel gating in CNGA1 channels.
  Eur Biophys J, 38, 465-478.  
18836841 A.V.Pischalnikova, and O.S.Sokolova (2009).
The domain and conformational organization in potassium voltage-gated ion channels.
  J Neuroimmune Pharmacol, 4, 71-82.  
18607586 D.Wray (2009).
Intracellular regions of potassium channels: Kv2.1 and heag.
  Eur Biophys J, 38, 285-292.  
19686652 H.Machiyama, H.Tatsumi, and M.Sokabe (2009).
Structural changes in the cytoplasmic domain of the mechanosensitive channel MscS during opening.
  Biophys J, 97, 1048-1057.  
19525958 J.W.Taraska, M.C.Puljung, N.B.Olivier, G.E.Flynn, and W.N.Zagotta (2009).
Mapping the structure and conformational movements of proteins with transition metal ion FRET.
  Nat Methods, 6, 532-537.
PDB codes: 3etq 3ffq
19172261 L.Stevens, M.Ju, and D.Wray (2009).
Roles of surface residues of intracellular domains of heag potassium channels.
  Eur Biophys J, 38, 523-532.  
19172259 M.Al-Owais, K.Bracey, and D.Wray (2009).
Role of intracellular domains in the function of the herg potassium channel.
  Eur Biophys J, 38, 569-576.  
19054768 M.Biel (2009).
Cyclic nucleotide-regulated cation channels.
  J Biol Chem, 284, 9017-9021.  
19544068 N.L.Wicks, K.S.Chan, Z.Madden, B.Santoro, and E.C.Young (2009).
Sensitivity of HCN channel deactivation to cAMP is amplified by an S4 mutation combined with activation mode shift.
  Pflugers Arch, 458, 877-889.  
19359484 N.Popovych, S.R.Tzeng, M.Tonelli, R.H.Ebright, and C.G.Kalodimos (2009).
Structural basis for cAMP-mediated allosteric control of the catabolite activator protein.
  Proc Natl Acad Sci U S A, 106, 6927-6932.
PDB code: 2wc2
19403523 R.Das, S.Chowdhury, M.T.Mazhab-Jafari, S.Sildas, R.Selvaratnam, and G.Melacini (2009).
Dynamically driven ligand selectivity in cyclic nucleotide binding domains.
  J Biol Chem, 284, 23682-23696.  
19465888 S.Schünke, M.Stoldt, K.Novak, U.B.Kaupp, and D.Willbold (2009).
Solution structure of the Mesorhizobium loti K1 channel cyclic nucleotide-binding domain in complex with cAMP.
  EMBO Rep, 10, 729-735.
PDB code: 2k0g
19368887 S.Warmuth, I.Zimmermann, and R.Dutzler (2009).
X-ray structure of the C-terminal domain of a prokaryotic cation-chloride cotransporter.
  Structure, 17, 538-546.
PDB code: 3g40
19671703 T.I.Brelidze, A.E.Carlson, and W.N.Zagotta (2009).
Absence of direct cyclic nucleotide modulation of mEAG1 and hERG1 channels revealed with fluorescence and electrophysiological methods.
  J Biol Chem, 284, 27989-27997.  
19748888 Y.C.Lin, J.Huang, H.Kan, J.C.Frisbee, and H.G.Yu (2009).
Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases.
  J Biol Chem, 284, 30433-30440.  
18375593 A.Barbuti, and D.DiFrancesco (2008).
Control of cardiac rate by "funny" channels in health and disease.
  Ann N Y Acad Sci, 1123, 213-223.  
18404204 A.P.Kornev, S.S.Taylor, and L.F.Ten Eyck (2008).
A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.
  PLoS Comput Biol, 4, e1000056.  
17931874 B.Tang, T.Sander, K.B.Craven, A.Hempelmann, and A.Escayg (2008).
Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy.
  Neurobiol Dis, 29, 59-70.  
18219271 D.Harzheim, K.H.Pfeiffer, L.Fabritz, E.Kremmer, T.Buch, A.Waisman, P.Kirchhof, U.B.Kaupp, and R.Seifert (2008).
Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP.
  EMBO J, 27, 692-703.  
18791833 G.Fernández-Ballester, and A.Ferrer-Montiel (2008).
Molecular modeling of the full-length human TRPV1 channel in closed and desensitized states.
  J Membr Biol, 223, 161-172.  
18223669 G.Heusch (2008).
Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents.
  Br J Pharmacol, 153, 1589-1601.  
18660803 H.Rehmann, E.Arias-Palomo, M.A.Hadders, F.Schwede, O.Llorca, and J.L.Bos (2008).
Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B.
  Nature, 455, 124-127.
PDB code: 3cf6
18621707 I.I.Serysheva, S.J.Ludtke, M.L.Baker, Y.Cong, M.Topf, D.Eramian, A.Sali, S.L.Hamilton, and W.Chiu (2008).
Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel.
  Proc Natl Acad Sci U S A, 105, 9610-9615.  
18643993 J.Baxter, W.Moeder, W.Urquhart, D.Shahinas, K.Chin, D.Christendat, H.G.Kang, M.Angelova, N.Kato, and K.Yoshioka (2008).
Identification of a functionally essential amino acid for Arabidopsis cyclic nucleotide gated ion channels using the chimeric AtCNGC11/12 gene.
  Plant J, 56, 457-469.  
18367452 K.B.Craven, N.B.Olivier, and W.N.Zagotta (2008).
C-terminal movement during gating in cyclic nucleotide-modulated channels.
  J Biol Chem, 283, 14728-14738.
PDB code: 3bpz
18458804 K.Bracey, M.Ju, C.Tian, L.Stevens, and D.Wray (2008).
Tubulin as a binding partner of the heag2 voltage-gated potassium channel.
  J Membr Biol, 222, 115-125.  
18212016 L.Zhou, and S.A.Siegelbaum (2008).
Effects of surface water on protein dynamics studied by a novel coarse-grained normal mode approach.
  Biophys J, 94, 3461-3474.  
18408037 L.Zhou, and S.A.Siegelbaum (2008).
Pathway and endpoint free energy calculations for cyclic nucleotide binding to HCN channels.
  Biophys J, 94, L90-L92.  
18094473 P.H.Zwart, R.W.Grosse-Kunstleve, A.A.Lebedev, G.N.Murshudov, and P.D.Adams (2008).
Surprises and pitfalls arising from (pseudo)symmetry.
  Acta Crystallogr D Biol Crystallogr, 64, 99.  
18619611 S.L.Altieri, G.M.Clayton, W.R.Silverman, A.O.Olivares, E.M.De la Cruz, L.R.Thomas, and J.H.Morais-Cabral (2008).
Structural and energetic analysis of activation by a cyclic nucleotide binding domain.
  J Mol Biol, 381, 655-669.
PDB codes: 3cl1 3clp 3co2
18167352 S.M.Harper, H.Wienk, R.W.Wechselberger, J.L.Bos, R.Boelens, and H.Rehmann (2008).
Structural dynamics in the activation of Epac.
  J Biol Chem, 283, 6501-6508.  
18456304 T.G.Wensel (2008).
Signal transducing membrane complexes of photoreceptor outer segments.
  Vision Res, 48, 2052-2061.  
18567637 V.Nache, J.Kusch, C.Biskup, E.Schulz, T.Zimmer, V.Hagen, and K.Benndorf (2008).
Thermodynamics of activation gating in olfactory-type cyclic nucleotide-gated (CNGA2) channels.
  Biophys J, 95, 2750-2758.  
  17591986 A.Bruening-Wright, F.Elinder, and H.P.Larsson (2007).
Kinetic relationship between the voltage sensor and the activation gate in spHCN channels.
  J Gen Physiol, 130, 71-81.  
17668006 A.Cukkemane, B.Grüter, K.Novak, T.Gensch, W.Bönigk, T.Gerharz, U.B.Kaupp, and R.Seifert (2007).
Subunits act independently in a cyclic nucleotide-activated K(+) channel.
  EMBO Rep, 8, 749-755.  
17044069 C.Anselmi, P.Carloni, and V.Torre (2007).
Origin of functional diversity among tetrameric voltage-gated channels.
  Proteins, 66, 136-146.  
17322905 C.Biskup, J.Kusch, E.Schulz, V.Nache, F.Schwede, F.Lehmann, V.Hagen, and K.Benndorf (2007).
Relating ligand binding to activation gating in CNGA2 channels.
  Nature, 446, 440-443.  
17521566 D.L.Minor (2007).
The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data.
  Neuron, 54, 511-533.  
17562314 G.E.Flynn, K.D.Black, L.D.Islas, B.Sankaran, and W.N.Zagotta (2007).
Structure and rearrangements in the carboxy-terminal region of SpIH channels.
  Structure, 15, 671-682.
PDB codes: 2ptm 2q0a
17183361 H.Rehmann, A.Wittinghofer, and J.L.Bos (2007).
Capturing cyclic nucleotides in action: snapshots from crystallographic studies.
  Nat Rev Mol Cell Biol, 8, 63-73.  
17622552 J.S.Bian, and T.V.McDonald (2007).
Phosphatidylinositol 4,5-bisphosphate interactions with the HERG K(+) channel.
  Pflugers Arch, 455, 105-113.  
17694071 J.W.Taraska, and W.N.Zagotta (2007).
Structural dynamics in the gating ring of cyclic nucleotide-gated ion channels.
  Nat Struct Mol Biol, 14, 854-860.  
17562313 L.Zhou, and S.A.Siegelbaum (2007).
Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy.
  Structure, 15, 655-670.  
17917115 M.Biel, and S.Michalakis (2007).
Function and dysfunction of CNG channels: insights from channelopathies and mouse models.
  Mol Neurobiol, 35, 266-277.  
17588940 M.M.Kuo, Y.Saimi, C.Kung, and S.Choe (2007).
Patch clamp and phenotypic analyses of a prokaryotic cyclic nucleotide-gated K+ channel using Escherichia coli as a host.
  J Biol Chem, 282, 24294-24301.  
17548815 S.Brauchi, G.Orta, C.Mascayano, M.Salazar, N.Raddatz, H.Urbina, E.Rosenmann, F.Gonzalez-Nilo, and R.Latorre (2007).
Dissection of the components for PIP2 activation and thermosensation in TRP channels.
  Proc Natl Acad Sci U S A, 104, 10246-10251.  
  17261842 S.Chen, J.Wang, L.Zhou, M.S.George, and S.A.Siegelbaum (2007).
Voltage sensor movement and cAMP binding allosterically regulate an inherently voltage-independent closed-open transition in HCN channels.
  J Gen Physiol, 129, 175-188.  
17914461 S.Herrmann, J.Stieber, G.Stöckl, F.Hofmann, and A.Ludwig (2007).
HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice.
  EMBO J, 26, 4423-4432.  
  17376843 S.Yang, and C.L.Cox (2007).
Modulation of inhibitory activity by nitric oxide in the thalamus.
  J Neurophysiol, 97, 3386-3395.  
17693406 V.P.Pau, Y.Zhu, Z.Yuchi, Q.Q.Hoang, and D.S.Yang (2007).
Characterization of the C-terminal domain of a potassium channel from Streptomyces lividans (KcsA).
  J Biol Chem, 282, 29163-29169.  
  17325193 W.Cheng, F.Yang, C.L.Takanishi, and J.Zheng (2007).
Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties.
  J Gen Physiol, 129, 191-207.  
  16735758 A.A.Fodor, and R.W.Aldrich (2006).
Statistical limits to the identification of ion channel domains by sequence similarity.
  J Gen Physiol, 127, 755-766.  
16538695 A.Mourot, T.Grutter, M.Goeldner, and F.Kotzyba-Hibert (2006).
Dynamic structural investigations on the torpedo nicotinic acetylcholine receptor by time-resolved photoaffinity labeling.
  Chembiochem, 7, 570-583.  
16273123 C.Altomare, A.Tognati, J.Bescond, A.Ferroni, and M.Baruscotti (2006).
Direct inhibition of the pacemaker (If) current in rabbit sinoatrial node cells by genistein.
  Br J Pharmacol, 147, 36-44.  
  16908727 D.L.Prole, and G.Yellen (2006).
Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and Post-S6.
  J Gen Physiol, 128, 273-282.  
17115052 E.A.Bykova, X.D.Zhang, T.Y.Chen, and J.Zheng (2006).
Large movement in the C terminus of CLC-0 chloride channel during slow gating.
  Nat Struct Mol Biol, 13, 1115-1119.  
16794778 F.Gambale, and N.Uozumi (2006).
Properties of shaker-type potassium channels in higher plants.
  J Membr Biol, 210, 1.  
16676167 F.Pena, B.Amuzescu, E.Neaga, and M.L.Flonta (2006).
Thermodynamic properties of hyperpolarization-activated current (Ih) in a subgroup of primary sensory neurons.
  Exp Brain Res, 173, 282-290.  
17178405 G.Zolles, N.Klöcker, D.Wenzel, J.Weisser-Thomas, B.K.Fleischmann, J.Roeper, and B.Fakler (2006).
Pacemaking by HCN channels requires interaction with phosphoinositides.
  Neuron, 52, 1027-1036.  
16791144 H.C.Lai, and L.Y.Jan (2006).
The distribution and targeting of neuronal voltage-gated ion channels.
  Nat Rev Neurosci, 7, 548-562.  
16452984 H.Rehmann, J.Das, P.Knipscheer, A.Wittinghofer, and J.L.Bos (2006).
Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state.
  Nature, 439, 625-628.
PDB code: 2byv
16962972 J.Yu, A.J.Yool, K.Schulten, and E.Tajkhorshid (2006).
Mechanism of gating and ion conductivity of a possible tetrameric pore in aquaporin-1.
  Structure, 14, 1411-1423.  
16460277 K.B.Craven, and W.N.Zagotta (2006).
CNG and HCN channels: two peas, one pod.
  Annu Rev Physiol, 68, 375-401.  
  16940556 L.D.Islas, and W.N.Zagotta (2006).
Short-range molecular rearrangements in ion channels detected by tryptophan quenching of bimane fluorescence.
  J Gen Physiol, 128, 337-346.  
16500960 M.Berrera, S.Pantano, and P.Carloni (2006).
cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations.
  Biophys J, 90, 3428-3433.  
16863470 P.J.Stansfeld, M.J.Sutcliffe, and J.S.Mitcheson (2006).
Molecular mechanisms for drug interactions with hERG that cause long QT syndrome.
  Expert Opin Drug Metab Toxicol, 2, 81-94.  
16715293 P.Mistrík, A.Pfeifer, and M.Biel (2006).
The enhancement of HCN channel instantaneous current facilitated by slow deactivation is regulated by intracellular chloride concentration.
  Pflugers Arch, 452, 718-727.  
17073662 R.L.Brown, T.Strassmaier, J.D.Brady, and J.W.Karpen (2006).
The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.
  Curr Pharm Des, 12, 3597-3613.  
16446144 Y.Chen, F.H.Yu, D.J.Surmeier, T.Scheuer, and W.A.Catterall (2006).
Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C.
  Neuron, 49, 409-420.  
17060318 Z.Z.Mei, R.Xia, D.J.Beech, and L.H.Jiang (2006).
Intracellular coiled-coil domain engaged in subunit interaction and assembly of melastatin-related transient receptor potential channel 2.
  J Biol Chem, 281, 38748-38756.  
15951376 A.Giorgetti, P.Carloni, P.Mistrik, and V.Torre (2005).
A homology model of the pore region of HCN channels.
  Biophys J, 89, 932-944.  
15644130 D.Bridges, M.E.Fraser, and G.B.Moorhead (2005).
Cyclic nucleotide binding proteins in the Arabidopsis thaliana and Oryza sativa genomes.
  BMC Bioinformatics, 6, 6.  
15618393 H.M.Berman, L.F.Ten Eyck, D.S.Goodsell, N.M.Haste, A.Kornev, and S.S.Taylor (2005).
The cAMP binding domain: an ancient signaling module.
  Proc Natl Acad Sci U S A, 102, 45-50.  
15710893 J.P.Johnson, and W.N.Zagotta (2005).
The carboxyl-terminal region of cyclic nucleotide-modulated channels is a gating ring, not a permeation path.
  Proc Natl Acad Sci U S A, 102, 2742-2747.  
16043489 J.Stieber, G.Stöckl, S.Herrmann, B.Hassfurth, and F.Hofmann (2005).
Functional expression of the human HCN3 channel.
  J Biol Chem, 280, 34635-34643.  
  15738051 L.Hua, and S.E.Gordon (2005).
Functional interactions between A' helices in the C-linker of open CNG channels.
  J Gen Physiol, 125, 335-344.  
15963351 M.Baruscotti, A.Bucchi, and D.Difrancesco (2005).
Physiology and pharmacology of the cardiac pacemaker ("funny") current.
  Pharmacol Ther, 107, 59-79.  
16026885 M.M.Kuo, W.J.Haynes, S.H.Loukin, C.Kung, and Y.Saimi (2005).
Prokaryotic K(+) channels: from crystal structures to diversity.
  FEMS Microbiol Rev, 29, 961-985.  
15923185 P.Mistrík, R.Mader, S.Michalakis, M.Weidinger, A.Pfeifer, and M.Biel (2005).
The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides.
  J Biol Chem, 280, 27056-27061.  
15749783 S.Haider, A.Grottesi, B.A.Hall, F.M.Ashcroft, and M.S.Sansom (2005).
Conformational dynamics of the ligand-binding domain of inward rectifier K channels as revealed by molecular dynamics simulations: toward an understanding of Kir channel gating.
  Biophys J, 88, 3310-3320.  
16084392 S.J.Ludtke, I.I.Serysheva, S.L.Hamilton, and W.Chiu (2005).
The pore structure of the closed RyR1 channel.
  Structure, 13, 1203-1211.  
16081488 V.Nache, E.Schulz, T.Zimmer, J.Kusch, C.Biskup, R.Koopmann, V.Hagen, and K.Benndorf (2005).
Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative.
  J Physiol, 569, 91.  
16079136 X.Zong, C.Eckert, H.Yuan, C.Wahl-Schott, H.Abicht, L.Fang, R.Li, P.Mistrik, A.Gerstner, B.Much, L.Baumann, S.Michalakis, R.Zeng, Z.Chen, and M.Biel (2005).
A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase.
  J Biol Chem, 280, 34224-34232.  
15128292 A.Ferrer-Montiel, C.García-Martínez, C.Morenilla-Palao, N.García-Sanz, A.Fernández-Carvajal, G.Fernández-Ballester, and R.Planells-Cases (2004).
Molecular architecture of the vanilloid receptor. Insights for drug design.
  Eur J Biochem, 271, 1820-1826.  
  15572342 A.L.Zimmerman (2004).
Capturing ion channel gating: a little salt on the tail does the trick.
  J Gen Physiol, 124, 627-629.  
  15337819 C.M.Nimigean, T.Shane, and C.Miller (2004).
A cyclic nucleotide modulated prokaryotic K+ channel.
  J Gen Physiol, 124, 203-210.  
15182710 D.M.Papazian (2004).
BK channels: the spring between sensor and gate.
  Neuron, 42, 699-701.  
14594805 E.C.Young, and N.Krougliak (2004).
Distinct structural determinants of efficacy and sensitivity in the ligand-binding domain of cyclic nucleotide-gated channels.
  J Biol Chem, 279, 3553-3562.  
15550244 G.M.Clayton, W.R.Silverman, L.Heginbotham, and J.H.Morais-Cabral (2004).
Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
  Cell, 119, 615-627.
PDB codes: 1u12 1vp6
15298894 I.Dreyer, F.Porée, A.Schneider, J.Mittelstädt, A.Bertl, H.Sentenac, J.B.Thibaud, and B.Mueller-Roeber (2004).
Assembly of plant Shaker-like K(out) channels requires two distinct sites of the channel alpha-subunit.
  Biophys J, 87, 858-872.  
  15337818 J.W.Karpen (2004).
Ion channel structure and the promise of bacteria: cyclic nucleotide-gated channels in the queue.
  J Gen Physiol, 124, 199-201.  
15274925 J.Wu, S.Brown, N.H.Xuong, and S.S.Taylor (2004).
RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site B.
  Structure, 12, 1057-1065.
PDB code: 1rl3
15134638 J.Zheng, and W.N.Zagotta (2004).
Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels.
  Neuron, 42, 411-421.  
  15572346 K.B.Craven, and W.N.Zagotta (2004).
Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels.
  J Gen Physiol, 124, 663-677.  
15572113 L.Zhou, N.B.Olivier, H.Yao, E.C.Young, and S.A.Siegelbaum (2004).
A conserved tripeptide in CNG and HCN channels regulates ligand gating by controlling C-terminal oligomerization.
  Neuron, 44, 823-834.  
  15314069 M.C.Trudeau, and W.N.Zagotta (2004).
Dynamics of Ca2+-calmodulin-dependent inhibition of rod cyclic nucleotide-gated channels measured by patch-clamp fluorometry.
  J Gen Physiol, 124, 211-223.  
14766177 M.S.Horning, and M.L.Mayer (2004).
Regulation of AMPA receptor gating by ligand binding core dimers.
  Neuron, 41, 379-388.  
14726518 N.Decher, J.Chen, and M.C.Sanguinetti (2004).
Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers.
  J Biol Chem, 279, 13859-13865.  
17173600 S.M.Brown, A.E.Dubin, and S.R.Chaplan (2004).
The role of pacemaker currents in neuropathic pain.
  Pain Pract, 4, 182-193.  
  14676284 S.Vemana, S.Pandey, and H.P.Larsson (2004).
S4 movement in a mammalian HCN channel.
  J Gen Physiol, 123, 21-32.  
15091336 T.Rosenbaum, and S.E.Gordon (2004).
Quickening the pace: looking into the heart of HCN channels.
  Neuron, 42, 193-196.  
14980206 W.Zhou, Y.Qian, K.Kunjilwar, P.J.Pfaffinger, and S.Choe (2004).
Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.
  Neuron, 41, 573-586.
PDB code: 1s6c
14659094 C.Ulens, and S.A.Siegelbaum (2003).
Regulation of hyperpolarization-activated HCN channels by cAMP through a gating switch in binding domain symmetry.
  Neuron, 40, 959-970.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.