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Night blindness causing G90D rhodopsin in complex with GaCT2 peptideNight blindness causing G90D rhodopsin in complex with GaCT2 peptide
Structural highlights
FunctionOPSD_BOVIN Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal (By similarity).[1] [2] Publication Abstract from PubMedWe 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. Insights into congenital stationary night blindness based on the structure of G90D rhodopsin.,Singhal A, Ostermaier MK, Vishnivetskiy SA, Panneels V, Homan KT, Tesmer JJ, Veprintsev D, Deupi X, Gurevich VV, Schertler GF, Standfuss J EMBO Rep. 2013 Apr 12. doi: 10.1038/embor.2013.44. PMID:23579341[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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