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Highly conserved tyrosine stabilizes the active state of rhodopsin

Goncalves, JA and South, K and Ahuja, S and Zaitseva, E and Opefi, CA and Eilers, M and Vogel, R and Reeves, PJ and Smith, SO (2010) 'Highly conserved tyrosine stabilizes the active state of rhodopsin.' Proceedings of the National Academy of Sciences of the United States of America, 107 (46). 19861 - 19866. ISSN 0027-8424

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Abstract

Light-induced isomerization of the 11-cis-retinal chromophore in the visual pigment rhodopsin triggers displacement of the second extracellular loop (EL2) and motion of transmembrane helices H5, H6, and H7 leading to the active intermediate metarhodopsin II (Meta II). We describe solid-state NMR measurements of rhodopsin and Meta II that target the molecular contacts in the region of the ionic lock involving these three helices. We show that a contact between Arg1353.50 and Met2576.40 forms in Meta II, consistent with the outward rotation of H6 and breaking of the dark-state Glu1343.49-Arg1353.50-Glu2476.30 ionic lock. We also show that Tyr2235.58 and Tyr3067.53 form molecular contacts with Met2576.40. Together these results reveal that the crystal structure of opsin in the region of the ionic lock reflects the active state of the receptor. We further demonstrate that Tyr2235.58 and Ala1323.47 in Meta II stabilize helix H5 in an active orientation. Mutation of Tyr2235.58 to phenylalanine or mutation of Ala132 3.47 to leucine decreases the lifetime of the Meta II intermediate. Furthermore, the Y223F mutation is coupled to structural changes in EL2. In contrast, mutation of Tyr3067.53 to phenylalanine shows only a moderate influence on the Meta II lifetime and is not coupled to EL2.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 07 Oct 2011 14:03
Last Modified: 14 Aug 2019 10:15
URI: http://repository.essex.ac.uk/id/eprint/927

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