4BEZ

Night blindness causing G90D rhodopsin in the active conformation

Summary for 4BEZ

• Entry DOI: 10.2210/pdb4bez/pdb
• Related: 4BEY
• Descriptor: RHODOPSIN, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ACETATE ION, ... (7 entities in total)
• Functional Keywords: membrane protein, gpcr, disease mutant, congential stationary night blindness, active state
• Biological source: BOS TAURUS (CATTLE)
• Cellular location: Membrane; Multi-pass membrane protein: P02699
• Total number of polymer chains: 1
• Total formula weight: 40545.20

Authors

Singhal, A.,Ostermaier, M.K.,Vishnivetskiy, S.A.,Panneels, V.,Homan, K.T.,Tesmer, J.J.G.,Veprintsev, D.,Deupi, X.,Gurevich, V.V.,Schertler, G.F.X.,Standfuss, J. (deposition date: 2013-03-12, release date: 2013-04-24, Last modification date: 2024-11-06)

Primary citation

Singhal, A.,Ostermaier, M.K.,Vishnivetskiy, S.A.,Panneels, V.,Homan, K.T.,Tesmer, J.J.,Veprintsev, D.,Deupi, X.,Gurevich, V.V.,Schertler, G.F.,Standfuss, J.
Insights Into Congenital Stationary Night Blindness Based on the Structure of G90D Rhodopsin.
Embo Rep., 14:520-, 2013

PubMed 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.

PubMed: 23579341
DOI: 10.1038/EMBOR.2013.44

Experimental method

X-RAY DIFFRACTION (3.3 Å)