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PMID: 11980705 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular architecture of a retinal cGMP-gated channel: the arrangement of the cytoplasmic domains.

The EMBO journal ·Vol. 21 ·No. 9 ·2002-05-01 ·Pages 2087-94

Higgins MK, Weitz D, Warne T, Schertler GF, Kaupp UB

Abstract

Cyclic nucleotide-gated (CNG) channels play a central role in the conversion of sensory information, such as light and scent, into primary electrical signals. We have purified the CNG channel from bovine retina and have studied it using electron microscopy and image processing. We present the structure of the channel to 35 A resolution. This three-dimensional reconstruction provides insight into the architecture of the protein, suggesting that the cyclic nucleotide-binding domains, which initiate the response to ligand, 'hang' below the pore-forming part of the channel, attached by narrow linkers. The structure also suggests that the four cyclic nucleotide-binding domains present in each channel form two distinct domains, lending structural weight to the suggestion that the four subunits of the CNG channels are arranged as a pair of dimers.

MeSH Terms
Animals Cattle Cyclic Nucleotide-Gated Cation Channels Ion Channels/chemistry,physiology,ultrastructure Protein Structure, Tertiary Protein Transport/physiology Rod Cell Outer Segment/chemistry,physiology Signal Transduction/physiology
Chemicals
Cyclic Nucleotide-Gated Cation Channels Ion Channels
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Higgins Matthew K
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Weitz Dietmar
Warne Tony
Schertler Gebhard F X
Kaupp U Benjamin
References (55)
55 references, click to expand
  1. Constraining the subunit order of rod cyclic nucleotide-gated channels reveals a diagonal arrangement of like subunits.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):895-900 PMID: 10639176
  2. A new subunit of the cyclic nucleotide-gated cation channel in retinal rods.
    Nature. 1993 Apr 22;362(6422):764-7 PMID: 7682292
  3. Two structural configurations of the skeletal muscle calcium release channel.
    Nat Struct Biol. 1996 Jun;3(6):547-52 PMID: 8646541
  4. MRC image processing programs.
    J Struct Biol. 1996 Jan-Feb;116(1):9-16 PMID: 8742717
  5. A new generation of the IMAGIC image processing system.
    J Struct Biol. 1996 Jan-Feb;116(1):17-24 PMID: 8742718
  6. Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy.
    Nature. 1997 Mar 6;386(6620):88-91 PMID: 9052786
  7. Structure of keyhole limpet hemocyanin type 1 (KLH1) at 15 A resolution by electron cryomicroscopy and angular reconstitution.
    J Mol Biol. 1997 Aug 22;271(3):417-37 PMID: 9268669
  8. Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels.
    Nature. 1993 Jul 1;364(6432):61-4 PMID: 7686276
  9. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
    Nature. 1994 May 26;369(6478):289-94 PMID: 8183366
  10. Probing the transmembrane topology of cyclic nucleotide-gated ion channels with a gene fusion approach.
    Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7425-9 PMID: 7543681
  11. Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels.
    Neuron. 1995 Sep;15(3):619-25 PMID: 7546741
  12. A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor.
    Neuron. 1995 Sep;15(3):627-36 PMID: 7546742
  13. Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10177-81 PMID: 7479749
  14. The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
    Science. 1998 Apr 3;280(5360):69-77 PMID: 9525859
  15. Identification of a domain on the beta-subunit of the rod cGMP-gated cation channel that mediates inhibition by calcium-calmodulin.
    J Biol Chem. 1998 Apr 10;273(15):9148-57 PMID: 9535905
  16. Calmodulin controls the rod photoreceptor CNG channel through an unconventional binding site in the N-terminus of the beta-subunit.
    EMBO J. 1998 Apr 15;17(8):2273-84 PMID: 9545240
  17. Crystal structure of the tetramerization domain of the Shaker potassium channel.
    Nature. 1998 Apr 30;392(6679):945-8 PMID: 9582078
  18. Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.
    Nat Genet. 1998 Jul;19(3):257-9 PMID: 9662398
  19. Constraining ligand-binding site stoichiometry suggests that a cyclic nucleotide-gated channel is composed of two functional dimers.
    Neuron. 1998 Jul;21(1):235-48 PMID: 9697867
  20. Structure of a glutamate-receptor ligand-binding core in complex with kainate.
    Nature. 1998 Oct 29;395(6705):913-7 PMID: 9804426
  21. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel.
    Science. 1998 Dec 18;282(5397):2220-6 PMID: 9856938
  22. Molecular determinants of a Ca2+-binding site in the pore of cyclic nucleotide-gated channels: S5/S6 segments control affinity of intrapore glutamates.
    EMBO J. 1999 Jan 4;18(1):119-30 PMID: 9878056
  23. Purification, characterization, and reconstitution of cyclic nucleotide-gated channels.
    Methods Enzymol. 1999;294:246-60 PMID: 9916231
  24. Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall.
    J Mol Biol. 1999 May 14;288(4):765-86 PMID: 10329178
  25. Stoichiometry and arrangement of subunits in rod cyclic nucleotide-gated channels.
    Neuron. 1999 Aug;23(4):809-19 PMID: 10482246
  26. Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
    Science. 2000 Jul 7;289(5476):123-7 PMID: 10884227
  27. Genetic basis of total colourblindness among the Pingelapese islanders.
    Nat Genet. 2000 Jul;25(3):289-93 PMID: 10888875
  28. Structural determinants of water permeation through aquaporin-1.
    Nature. 2000 Oct 5;407(6804):599-605 PMID: 11034202
  29. Structure of a glycerol-conducting channel and the basis for its selectivity.
    Science. 2000 Oct 20;290(5491):481-6 PMID: 11039922
  30. Projection structure of a ClC-type chloride channel at 6.5 A resolution.
    Nature. 2001 Jan 11;409(6817):219-23 PMID: 11196649
  31. Change of pore helix conformational state upon opening of cyclic nucleotide-gated channels.
    Neuron. 2000 Dec;28(3):899-909 PMID: 11163275
  32. The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities.
    Nature. 2001 Feb 22;409(6823):1047-51 PMID: 11234014
  33. Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel.
    Neuron. 2001 Mar;29(3):593-601 PMID: 11301020
  34. Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin.
    Nature. 2001 Apr 26;410(6832):1120-4 PMID: 11323678
  35. Direct evidence for the size and conformational variability of the pyruvate dehydrogenase complex revealed by three-dimensional electron microscopy. The "breathing" core and its functional relationship to protein dynamics.
    J Biol Chem. 2001 Jun 15;276(24):21704-13 PMID: 11285267
  36. A functioning chimera of the cyclic nucleotide-binding domain from the bovine retinal rod ion channel and the DNA-binding domain from catabolite gene-activating protein.
    Biochemistry. 2001 Jun 26;40(25):7464-73 PMID: 11412099
  37. Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels.
    Neuron. 2001 Jun;30(3):689-98 PMID: 11430803
  38. Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution.
    Structure. 2001 Mar 7;9(3):215-20 PMID: 11286888
  39. Rotational movement during cyclic nucleotide-gated channel opening.
    Nature. 2001 Aug 30;412(6850):917-21 PMID: 11528481
  40. Cyclic nucleotide-gated channels: shedding light on the opening of a channel pore.
    Nat Rev Neurosci. 2001 Sep;2(9):643-51 PMID: 11533732
  41. The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes.
    J Biol Chem. 2001 Dec 21;276(51):48009-16 PMID: 11641407
  42. X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
    Nature. 2002 Jan 17;415(6869):287-94 PMID: 11796999
  43. An equilibrium study of the cooperative binding of adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate to the adenosine cyclic 3',5'-monophosphate receptor protein from Escherichia coli.
    Biochemistry. 1980 Oct 28;19(22):5124-30 PMID: 6257276
  44. Isolation and characterization of osmotically sealed bovine rod outer segments.
    Methods Enzymol. 1982;81:110-6 PMID: 7098855
  45. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.
    Nature. 1985 Jan 24-30;313(6000):310-3 PMID: 2578616
  46. Identification, purification, and functional reconstitution of the cyclic GMP-dependent channel from rod photoreceptors.
    Proc Natl Acad Sci U S A. 1987 Jan;84(2):585-9 PMID: 2432613
  47. A cyclic nucleotide-gated conductance in olfactory receptor cilia.
    Nature. 1987 Jan 29-Feb 4;325(6103):442-4 PMID: 3027574
  48. Structure of a complex of catabolite gene activator protein and cyclic AMP refined at 2.5 A resolution.
    J Mol Biol. 1987 Nov 20;198(2):311-26 PMID: 2828639
  49. Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
    Nature. 1989 Dec 14;342(6251):762-6 PMID: 2481236
  50. Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9868-72 PMID: 1719541
  51. Antibodies against synthetic peptides used to determine the topology and site of glycosylation of the cGMP-gated channel from bovine rod photoreceptors.
    J Biol Chem. 1992 Jan 5;267(1):644-8 PMID: 1370452
  52. Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.
    Science. 1992 Aug 28;257(5074):1225-30 PMID: 1519059
  53. A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels.
    Science. 1992 Nov 13;258(5085):1152-5 PMID: 1279807
  54. Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin.
    Nature. 1993 Jan 7;361(6407):76-9 PMID: 7678445
  55. Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.
    Neuron. 1996 May;16(5):983-90 PMID: 8630256
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/21.9.2087
Published
2002-05-01
Pages
2087-94
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125374
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/21.9.2087 PMC Full Text View journal details
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