Home LiteratureArticle Details
PMID: 15220479 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Coupling of retinal isomerization to the activation of rhodopsin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 27 ·2004-07-06 ·Pages 10048-53

Patel AB, Crocker E, Eilers M, Hirshfeld A, Sheves M, Smith SO

Abstract

Activation of the visual pigment rhodopsin is caused by 11-cis to -trans isomerization of its retinal chromophore. High-resolution solid-state NMR measurements on both rhodopsin and the metarhodopsin II intermediate show how retinal isomerization disrupts helix interactions that lock the receptor off in the dark. We made 2D dipolar-assisted rotational resonance NMR measurements between (13)C-labels on the retinal chromophore and specific (13)C-labels on tyrosine, glycine, serine, and threonine in the retinal binding site of rhodopsin. The essential aspects of the isomerization trajectory are a large rotation of the C20 methyl group toward extracellular loop 2 and a 4- to 5-A translation of the retinal chromophore toward transmembrane helix 5. The retinal-protein contacts observed in the active metarhodopsin II intermediate suggest a general activation mechanism for class A G protein-coupled receptors involving coupled motion of transmembrane helices 5, 6, and 7.

MeSH Terms
Binding Sites Isomerism Nuclear Magnetic Resonance, Biomolecular Protein Structure, Secondary Retinaldehyde/chemistry Rhodopsin/analogs & derivatives,chemistry,metabolism
Chemicals
metarhodopsins Rhodopsin Retinaldehyde
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Patel Ashish B
Department of Physiology and Biophysics, Center for Structural Biology, Stony Brook University, NY 11794-5215, USA.
Crocker Evan
Eilers Markus
Hirshfeld Amiram
Sheves Mordechai
Smith Steven O
References (39)
39 references, click to expand
  1. Dipolar assisted rotational resonance NMR of tryptophan and tyrosine in rhodopsin.
    J Biomol NMR. 2004 May;29(1):11-20 PMID: 15017136
  2. Conformational similarities in the beta-ionone ring region of the rhodopsin chromophore in its ground state and after photoactivation to the metarhodopsin-I intermediate.
    Biochemistry. 2003 Nov 25;42(46):13371-8 PMID: 14621981
  3. Identification of core amino acids stabilizing rhodopsin.
    Proc Natl Acad Sci U S A. 2004 May 11;101(19):7246-51 PMID: 15123809
  4. The spectral properties of some visual pigment analogs.
    Exp Eye Res. 1973 Dec 24;17(6):591-606 PMID: 4798751
  5. 13C NMR spectroscopy of the chromophore of rhodopsin.
    Methods Enzymol. 1982;81:698-703 PMID: 7098911
  6. Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor.
    J Biol Chem. 1989 Aug 15;264(23):13572-8 PMID: 2547766
  7. Role of the intradiscal domain in rhodopsin assembly and function.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):4991-5 PMID: 2367520
  8. Solid-state 13C NMR study of tyrosine protonation in dark-adapted bacteriorhodopsin.
    Biochemistry. 1990 Jun 12;29(23):5567-74 PMID: 2167129
  9. Mapping of the amino acids in membrane-embedded helices that interact with the retinal chromophore in bovine rhodopsin.
    J Biol Chem. 1991 Mar 5;266(7):4269-75 PMID: 1999419
  10. Identification of residues important for ligand binding to the human 5-hydroxytryptamine1A serotonin receptor.
    Mol Pharmacol. 1993 Apr;43(4):516-20 PMID: 8474430
  11. Interactions of the beta-ionone ring with the protein in the visual pigment rhodopsin control the activation mechanism. An FTIR and fluorescence study on artificial vertebrate rhodopsins.
    Biochemistry. 1994 Jun 14;33(23):7389-97 PMID: 8003504
  12. Structure and function in rhodopsin. Measurement of the rate of metarhodopsin II decay by fluorescence spectroscopy.
    J Biol Chem. 1995 Mar 10;270(10):5073-6 PMID: 7890614
  13. Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F.
    Nature. 1996 Sep 26;383(6598):347-50 PMID: 8848049
  14. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin.
    Science. 1996 Nov 1;274(5288):768-70 PMID: 8864113
  15. Structure and function in rhodopsin: high level expression of a synthetic bovine opsin gene and its mutants in stable mammalian cell lines.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11487-92 PMID: 8876162
  16. Occluded molecular surface: analysis of protein packing.
    J Mol Recognit. 1995 Nov-Dec;8(6):334-44 PMID: 9052974
  17. Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: expression of 15N-lysine- and 13C-glycine-labeled opsin in a stable cell line.
    Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):487-92 PMID: 9892660
  18. Vertebrate lumi- and meta-rhodopsins.
    Nature. 1959 Feb 14;183(4659):442-6 PMID: 13632749
  19. Plaque production by the polyoma virus.
    Virology. 1959 Jul;8(3):396-7 PMID: 13669362
  20. Pre-lumirhodopsin and the bleaching of visual pigments.
    Nature. 1963 Mar 30;197:1279-86 PMID: 14002749
  21. Interconversion of metarhodopsins I and II: a branched photointermediate decay model.
    Biochemistry. 1990 Oct 2;29(39):9135-42 PMID: 2271583
  22. Uncovering molecular mechanisms involved in activation of G protein-coupled receptors.
    Endocr Rev. 2000 Feb;21(1):90-113 PMID: 10696571
  23. Movement of retinal along the visual transduction path.
    Science. 2000 Jun 23;288(5474):2209-12 PMID: 10864869
  24. Signaling states of rhodopsin. Retinal provides a scaffold for activating proton transfer switches.
    J Biol Chem. 2000 Jun 30;275(26):19713-8 PMID: 10770924
  25. The molecular origin of the inhibition of transducin activation in rhodopsin lacking the 9-methyl group of the retinal chromophore: a UV-Vis and FTIR spectroscopic study.
    Biochemistry. 2000 Aug 1;39(30):8895-908 PMID: 10913302
  26. Crystal structure of rhodopsin: A G protein-coupled receptor.
    Science. 2000 Aug 4;289(5480):739-45 PMID: 10926528
  27. The forgotten serine. A critical role for Ser-2035.42 in ligand binding to and activation of the beta 2-adrenergic receptor.
    J Biol Chem. 2000 Dec 1;275(48):37779-88 PMID: 10964911
  28. Magic angle spinning nuclear magnetic resonance of isotopically labeled rhodopsin.
    Methods Enzymol. 2002;343:212-22 PMID: 11675791
  29. Motifs of serine and threonine can drive association of transmembrane helices.
    J Mol Biol. 2002 Feb 22;316(3):799-805 PMID: 11866532
  30. Comparison of helix interactions in membrane and soluble alpha-bundle proteins.
    Biophys J. 2002 May;82(5):2720-36 PMID: 11964258
  31. Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5982-7 PMID: 11972040
  32. Structure and function in rhodopsin: a tetracycline-inducible system in stable mammalian cell lines for high-level expression of opsin mutants.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13413-8 PMID: 12370422
  33. Beta2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch.
    J Biol Chem. 2002 Oct 25;277(43):40989-96 PMID: 12167654
  34. Activation of the cannabinoid CB1 receptor may involve a W6 48/F3 36 rotamer toggle switch.
    J Pept Res. 2002 Dec;60(6):357-70 PMID: 12464114
  35. Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2290-5 PMID: 12601165
  36. Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking.
    Adv Protein Chem. 2003;63:243-90 PMID: 12629973
  37. Retinal counterion switch in the photoactivation of the G protein-coupled receptor rhodopsin.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9262-7 PMID: 12835420
  38. Assessing structural elements that influence Schiff base stability: mutants E113Q and D190N destabilize rhodopsin through different mechanisms.
    Vision Res. 2003 Dec;43(28):2991-3002 PMID: 14611935
  39. Helix packing moments reveal diversity and conservation in membrane protein structure.
    J Mol Biol. 2004 Mar 26;337(3):713-29 PMID: 15019789
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
0027-8424
DOI
10.1073/pnas.0402848101
Published
2004-07-06
Epub
2004-00-25
Pages
10048-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC454162
Subset
IM
Grants
NIGMS NIH HHS · R01 GM041412 · United States
NIGMS NIH HHS · GM-41412 · United States
NCRR NIH HHS · S10 RR13889 · United States
External Links
PubMed source DOI: 10.1073/pnas.0402848101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2