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.
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Authors | Ankita 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 |
Journal | EMBO reports
(EMBO Rep)
Vol. 14
Issue 6
Pg. 520-6
(Jun 2013)
ISSN: 1469-3178 [Electronic] England |
PMID | 23579341
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Arrestin
- Schiff Bases
- Rhodopsin
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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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