title: 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.
authors.affiliation: Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen 5232, Switzerland.
authors.forename: Ankita
authors.initials: A
authors.lastname: Singhal
authors.forename: Martin K
authors.initials: MK
authors.lastname: Ostermaier
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: Valérie
authors.initials: V
authors.lastname: Panneels
authors.forename: Kristoff T
authors.initials: KT
authors.lastname: Homan
authors.forename: John J G
authors.initials: JJ
authors.lastname: Tesmer
authors.forename: Dmitry
authors.initials: D
authors.lastname: Veprintsev
authors.forename: Xavier
authors.initials: X
authors.lastname: Deupi
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
authors.forename: Gebhard F X
authors.initials: GF
authors.lastname: Schertler
authors.forename: Joerg
authors.initials: J
authors.lastname: Standfuss
mesh_terms: D019393:Arrestin / Q000737:chemistry; D018360:Crystallography, X-Ray; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D009216:Myopia / Q000235:genetics*; D009755:Night Blindness / Q000235:genetics*; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics; D012545:Schiff Bases; D040681:Structural Homology, Protein; D044366:Transition Temperature
chemical_list: D019393:Arrestin; D012545:Schiff Bases; D012243:Rhodopsin