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PMID: 23579341 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Insights into congenital stationary night blindness based on the structure of G90D rhodopsin.

EMBO reports ·Vol. 14 ·No. 6 ·2013-06-00 ·Pages 520-6

Singhal A, Ostermaier MK, Vishnivetskiy SA, Panneels V, Homan KT, Tesmer JJ, Veprintsev D, Deupi X, Gurevich VV, Schertler GF, Standfuss J

Abstract

We present active-state structures of the G protein-coupled receptor (GPCRs) rhodopsin carrying the disease-causing mutation G90D. Mutations of G90 cause either retinitis pigmentosa (RP) or congenital stationary night blindness (CSNB), a milder, non-progressive form of RP. Our analysis shows that the CSNB-causing G90D mutation introduces a salt bridge with K296. The mutant thus interferes with the E113Q-K296 activation switch and the covalent binding of the inverse agonist 11-cis-retinal, two interactions that are crucial for the deactivation of rhodopsin. Other mutations, including G90V causing RP, cannot promote similar interactions. We discuss our findings in context of a model in which CSNB is caused by constitutive activation of the visual signalling cascade.

MeSH Terms
Arrestin/chemistry Crystallography, X-Ray Eye Diseases, Hereditary/genetics Genetic Diseases, X-Linked/genetics HEK293 Cells Humans Models, Molecular Mutation, Missense Myopia/genetics Night Blindness/genetics Protein Binding Protein Stability Protein Structure, Secondary Protein Structure, Tertiary Rhodopsin/chemistry,genetics Schiff Bases Structural Homology, Protein Transition Temperature
Chemicals
Arrestin Schiff Bases Rhodopsin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Singhal Ankita
Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen 5232, Switzerland.
Ostermaier Martin K
Vishnivetskiy Sergey A
Panneels Valérie
Homan Kristoff T
Tesmer John J G
Veprintsev Dmitry
Deupi Xavier
Gurevich Vsevolod V
Schertler Gebhard F X
Standfuss Joerg
Supplementary Concepts
Night blindness, congenital stationary (Disease)
References (35)
35 references, click to expand
  1. Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process.
    Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18690-5 PMID: 22039220
  2. Molecular mechanisms of rhodopsin retinitis pigmentosa and the efficacy of pharmacological rescue.
    J Mol Biol. 2010 Feb 5;395(5):1063-78 PMID: 19913029
  3. Biased signaling pathways in β2-adrenergic receptor characterized by 19F-NMR.
    Science. 2012 Mar 2;335(6072):1106-10 PMID: 22267580
  4. Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness.
    Nat Genet. 1997 Feb;15(2):175-8 PMID: 9020843
  5. 11-cis- and all-trans-retinols can activate rod opsin: rational design of the visual cycle.
    Biochemistry. 2008 Jul 15;47(28):7567-71 PMID: 18563917
  6. Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II.
    Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):119-24 PMID: 22198838
  7. Slow binding of retinal to rhodopsin mutants G90D and T94D.
    Biochemistry. 2003 Feb 25;42(7):2002-8 PMID: 12590587
  8. Crystal structure of metarhodopsin II.
    Nature. 2011 Mar 31;471(7340):651-5 PMID: 21389988
  9. Two protonation switches control rhodopsin activation in membranes.
    Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17795-800 PMID: 18997017
  10. Constitutive activation of opsin: interaction of mutants with rhodopsin kinase and arrestin.
    Biochemistry. 1995 Sep 19;34(37):11938-45 PMID: 7547930
  11. Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness.
    Nature. 1994 Feb 17;367(6464):639-42 PMID: 8107847
  12. The structural basis of agonist-induced activation in constitutively active rhodopsin.
    Nature. 2011 Mar 31;471(7340):656-60 PMID: 21389983
  13. Night blindness and the mechanism of constitutive signaling of mutant G90D rhodopsin.
    J Neurosci. 2008 Nov 5;28(45):11662-72 PMID: 18987202
  14. Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes.
    Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1630-5 PMID: 16565402
  15. Crystal structures of a stabilized β1-adrenoceptor bound to the biased agonists bucindolol and carvedilol.
    Structure. 2012 May 9;20(5):841-9 PMID: 22579251
  16. Site of G protein binding to rhodopsin mapped with synthetic peptides from the alpha subunit.
    Science. 1988 Aug 12;241(4867):832-5 PMID: 3136547
  17. Crystal structure of the ligand-free G-protein-coupled receptor opsin.
    Nature. 2008 Jul 10;454(7201):183-7 PMID: 18563085
  18. Crystal structure of a thermally stable rhodopsin mutant.
    J Mol Biol. 2007 Oct 5;372(5):1179-88 PMID: 17825322
  19. Molecular mechanisms of disease for mutations at Gly-90 in rhodopsin.
    J Biol Chem. 2011 Nov 18;286(46):39993-40001 PMID: 21940625
  20. Effect of channel mutations on the uptake and release of the retinal ligand in opsin.
    Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5247-52 PMID: 22431612
  21. Role of noncovalent binding of 11-cis-retinal to opsin in dark adaptation of rod and cone photoreceptors.
    Neuron. 2001 Mar;29(3):749-55 PMID: 11301033
  22. A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese.
    Nat Genet. 1995 Jul;10(3):360-2 PMID: 7670478
  23. Dark-light: model for nightblindness from the human rhodopsin Gly-90-->Asp mutation.
    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):880-4 PMID: 7846071
  24. Characterization of rhodopsin congenital night blindness mutant T94I.
    Biochemistry. 2003 Feb 25;42(7):2009-15 PMID: 12590588
  25. Thermal properties of rhodopsin: insight into the molecular mechanism of dim-light vision.
    J Biol Chem. 2011 Aug 5;286(31):27622-9 PMID: 21659526
  26. Opsin activation as a cause of congenital night blindness.
    Nat Neurosci. 2003 Jul;6(7):731-5 PMID: 12778053
  27. Effect of carboxylic acid side chains on the absorption maximum of visual pigments.
    Science. 1989 Nov 17;246(4932):928-30 PMID: 2573154
  28. Structure of bovine rhodopsin in a trigonal crystal form.
    J Mol Biol. 2004 Nov 5;343(5):1409-38 PMID: 15491621
  29. Structure and function in rhodopsin: rhodopsin mutants with a neutral amino acid at E134 have a partially activated conformation in the dark state.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14273-8 PMID: 9405602
  30. Characterization of the mutant visual pigment responsible for congenital night blindness: a biochemical and Fourier-transform infrared spectroscopy study.
    Biochemistry. 1996 Jun 11;35(23):7536-45 PMID: 8652533
  31. Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6.
    Biochemistry. 1998 Jun 2;37(22):8253-61 PMID: 9609722
  32. Structural origins of constitutive activation in rhodopsin: Role of the K296/E113 salt bridge.
    Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12508-13 PMID: 15306683
  33. Constitutive "light" adaptation in rods from G90D rhodopsin: a mechanism for human congenital nightblindness without rod cell loss.
    J Neurosci. 2001 Aug 1;21(15):5449-60 PMID: 11466416
  34. 1 rhodopsin mutations in congenital night blindness.
    Adv Exp Med Biol. 2010;664:263-72 PMID: 20238025
  35. Monomeric rhodopsin is sufficient for normal rhodopsin kinase (GRK1) phosphorylation and arrestin-1 binding.
    J Biol Chem. 2011 Jan 14;286(2):1420-8 PMID: 20966068
Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-3178
DOI
10.1038/embor.2013.44
Published
2013-06-00
Epub
2013-00-12
Pages
520-6
Language
English
Region
England
NLM ID
100963049
PMCID
PMC3674435
Subset
IM
Grants
NHLBI NIH HHS · HL071818 · United States
NEI NIH HHS · EY011500 · United States
NHLBI NIH HHS · R01 HL086865 · United States
NEI NIH HHS · R01 EY011500 · United States
NHLBI NIH HHS · R01 HL071818 · United States
External Links
PubMed source DOI: 10.1038/embor.2013.44 PMC Full Text View journal details
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