Journal
EMBO REPORTS
Volume 14, Issue 6, Pages 520-526Publisher
WILEY
DOI: 10.1038/embor.2013.44
Keywords
G protein-coupled receptors; biased signalling; rhodopsin; congenital stationary night blindness; retinitis pigmentosa
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Funding
- Swiss National Science Foundation [31003A_132815, 31003A_141235]
- National Center for Competence in Research in Structural Biology Program
- National Institutes of Health [EY011500, HL071818]
- Swiss National Science Foundation (SNF) [31003A_141235, 31003A_132815] Funding Source: Swiss National Science Foundation (SNF)
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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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