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PMID: 18490661 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structure of TRPV1 channel revealed by electron cryomicroscopy.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 21 ·2008-05-27 ·Pages 7451-5

Moiseenkova-Bell VY, Stanciu LA, Serysheva II, Tobe BJ, Wensel TG

Abstract

The transient receptor potential (TRP) family of ion channels participate in many signaling pathways. TRPV1 functions as a molecular integrator of noxious stimuli, including heat, low pH, and chemical ligands. Here, we report the 3D structure of full-length rat TRPV1 channel expressed in the yeast Saccharomyces cerevisiae and purified by immunoaffinity chromatography. We demonstrate that the recombinant purified TRPV1 channel retains its structural and functional integrity and is suitable for structural analysis. The 19-A structure of TRPV1 determined by using single-particle electron cryomicroscopy exhibits fourfold symmetry and comprises two distinct regions: a large open basket-like domain, likely corresponding to the cytoplasmic N- and C-terminal portions, and a more compact domain, corresponding to the transmembrane portion. The assignment of transmembrane and cytoplasmic regions was supported by fitting crystal structures of the structurally homologous Kv1.2 channel and isolated TRPV1 ankyrin repeats into the TRPV1 structure.

MeSH Terms
Animals Ankyrin Repeat Cell Membrane/chemistry Cryoelectron Microscopy/methods Crystallography Cytoplasm/chemistry Imaging, Three-Dimensional Kv1.2 Potassium Channel/chemistry Protein Conformation Rats Recombinant Proteins/chemistry,genetics,isolation & purification Saccharomyces cerevisiae/genetics TRPV Cation Channels/chemistry,genetics,isolation & purification
Chemicals
Kv1.2 Potassium Channel Recombinant Proteins TRPV Cation Channels Trpv1 protein, rat
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Moiseenkova-Bell Vera Y
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Stanciu Lia A
Serysheva Irina I
Tobe Ben J
Wensel Theodore G
References (43)
43 references, click to expand
  1. Crystal structure and mechanism of a calcium-gated potassium channel.
    Nature. 2002 May 30;417(6888):515-22 PMID: 12037559
  2. Tertiary interactions between transmembrane segments 3 and 5 near the cytoplasmic side of rhodopsin.
    Biochemistry. 1999 Sep 14;38(37):12033-40 PMID: 10508407
  3. Cryo-electron microscopy of vitrified specimens.
    Q Rev Biophys. 1988 May;21(2):129-228 PMID: 3043536
  4. Kinetics of calcium channel opening by inositol 1,4,5-trisphosphate.
    Biochemistry. 1990 Jan 9;29(1):32-7 PMID: 1691015
  5. Structure of the type 1 inositol 1,4,5-trisphosphate receptor revealed by electron cryomicroscopy.
    J Biol Chem. 2003 Jun 13;278(24):21319-22 PMID: 12714606
  6. The cloned capsaicin receptor integrates multiple pain-producing stimuli.
    Neuron. 1998 Sep;21(3):531-43 PMID: 9768840
  7. X-ray structure of a voltage-dependent K+ channel.
    Nature. 2003 May 1;423(6935):33-41 PMID: 12721618
  8. Abnormal electroretinogram from a Drosophila mutant.
    Nature. 1969 Oct 18;224(5216):285-7 PMID: 5344615
  9. Use of chemical chaperones in the yeast Saccharomyces cerevisiae to enhance heterologous membrane protein expression: high-yield expression and purification of human P-glycoprotein.
    Arch Biochem Biophys. 2000 Apr 1;376(1):34-46 PMID: 10729188
  10. Localization of binding sites for carboxyl terminal specific anti-rhodopsin monoclonal antibodies using synthetic peptides.
    Biochemistry. 1984 Dec 18;23(26):6544-9 PMID: 6529569
  11. TRP channels as cellular sensors.
    Nature. 2003 Dec 4;426(6966):517-24 PMID: 14654832
  12. Monoclonal antibodies to rhodopsin: characterization, cross-reactivity, and application as structural probes.
    Biochemistry. 1983 Feb 1;22(3):653-60 PMID: 6188482
  13. Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution.
    Structure. 2001 Mar 7;9(3):215-20 PMID: 11286888
  14. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
    Science. 2005 Aug 5;309(5736):897-903 PMID: 16002581
  15. Permeation and selectivity of TRP channels.
    Annu Rev Physiol. 2006;68:685-717 PMID: 16460288
  16. EMAN: semiautomated software for high-resolution single-particle reconstructions.
    J Struct Biol. 1999 Dec 1;128(1):82-97 PMID: 10600563
  17. Analysis of the native quaternary structure of vanilloid receptor 1.
    J Biol Chem. 2001 Jul 27;276(30):28613-9 PMID: 11358970
  18. The non-selective cation-permeable channel TRPC3 is a tetrahedron with a cap on the large cytoplasmic end.
    Biochem Biophys Res Commun. 2005 Aug 5;333(3):768-77 PMID: 15964551
  19. 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
  20. Capsaicin receptor in the pain pathway.
    Jpn J Pharmacol. 2000 May;83(1):20-4 PMID: 10887936
  21. Crystal structure of the human TRPV2 channel ankyrin repeat domain.
    Protein Sci. 2006 Sep;15(9):2201-6 PMID: 16882997
  22. Sensing with TRP channels.
    Nat Chem Biol. 2005 Jul;1(2):85-92 PMID: 16408004
  23. Conformational changes in the C terminus of Shaker K+ channel bound to the rat Kvbeta2-subunit.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12607-12 PMID: 14569011
  24. The pore structure of the closed RyR1 channel.
    Structure. 2005 Aug;13(8):1203-11 PMID: 16084392
  25. Structure of cation channels, revealed by single particle electron microscopy.
    FEBS Lett. 2004 Apr 30;564(3):251-6 PMID: 15111105
  26. TRP channels: a TR(I)P through a world of multifunctional cation channels.
    Pflugers Arch. 2005 Oct;451(1):1-10 PMID: 16012814
  27. Trp ion channels and temperature sensation.
    Annu Rev Neurosci. 2006;29:135-61 PMID: 16776582
  28. The capsaicin receptor: a heat-activated ion channel in the pain pathway.
    Nature. 1997 Oct 23;389(6653):816-24 PMID: 9349813
  29. The structure of the prokaryotic cyclic nucleotide-modulated potassium channel MloK1 at 16 A resolution.
    Structure. 2007 Sep;15(9):1053-64 PMID: 17850745
  30. The TRP superfamily of cation channels.
    Sci STKE. 2005 Feb 22;2005(272):re3 PMID: 15728426
  31. Overexpression and purification of the vanilloid receptor in yeast (Saccharomyces cerevisiae).
    Biochem Biophys Res Commun. 2003 Oct 10;310(1):196-201 PMID: 14511670
  32. TRP channel proteins and signal transduction.
    Physiol Rev. 2002 Apr;82(2):429-72 PMID: 11917094
  33. The vanilloid receptor: a molecular gateway to the pain pathway.
    Annu Rev Neurosci. 2001;24:487-517 PMID: 11283319
  34. Structure-function analysis of TRPV channels.
    Naunyn Schmiedebergs Arch Pharmacol. 2005 Apr;371(4):285-94 PMID: 15889240
  35. Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
    Science. 2000 Apr 14;288(5464):306-13 PMID: 10764638
  36. Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel.
    J Biol Chem. 2006 Sep 1;281(35):25006-10 PMID: 16809337
  37. The motor protein prestin is a bullet-shaped molecule with inner cavities.
    J Biol Chem. 2008 Jan 11;283(2):1137-45 PMID: 17998209
  38. The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
    Science. 1998 Apr 3;280(5360):69-77 PMID: 9525859
  39. The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas.
    J Mol Biol. 2007 Mar 23;367(2):373-83 PMID: 17258231
  40. Three-dimensional reconstruction using transmission electron microscopy reveals a swollen, bell-shaped structure of transient receptor potential melastatin type 2 cation channel.
    J Biol Chem. 2007 Dec 21;282(51):36961-70 PMID: 17940282
  41. The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
    Neuron. 2007 Jun 21;54(6):905-18 PMID: 17582331
  42. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction.
    Neuron. 1989 Apr;2(4):1313-23 PMID: 2516726
  43. Molecular architecture of a retinal cGMP-gated channel: the arrangement of the cytoplasmic domains.
    EMBO J. 2002 May 1;21(9):2087-94 PMID: 11980705
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0711835105
Published
2008-05-27
Epub
2008-00-19
Pages
7451-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2396679
Subset
IM
Grants
NIGMS NIH HHS · R01 GM072804 · United States
NCRR NIH HHS · P41-RR02250 · United States
NCRR NIH HHS · P41 RR002250 · United States
NIDDK NIH HHS · R90 DK071505 · United States
NEI NIH HHS · R01-EY07981 · United States
NIGMS NIH HHS · R01-GM072804 · United States
NIGMS NIH HHS · P01-GM99116 · United States
NEI NIH HHS · R01 EY007981 · United States
NIDDK NIH HHS · T90-DK071505 · United States
External Links
PubMed source DOI: 10.1073/pnas.0711835105 PMC Full Text View journal details
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