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

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.
AuthorsAnkita Singhal, Martin K Ostermaier, Sergey A Vishnivetskiy, Valérie Panneels, Kristoff T Homan, John J G Tesmer, Dmitry Veprintsev, Xavier Deupi, Vsevolod V Gurevich, Gebhard F X Schertler, Joerg Standfuss
JournalEMBO reports (EMBO Rep) Vol. 14 Issue 6 Pg. 520-6 (Jun 2013) ISSN: 1469-3178 [Electronic] England
PMID23579341 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Arrestin
  • Schiff Bases
  • Rhodopsin
Topics
  • 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

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