A methyl group at C7 of 11-cis-retinal allows chromophore formation but affects rhodopsin activation
نویسندگان
چکیده
The newly synthesized 11-cis-7-methylretinal can form an artificial visual pigment with kinetic and spectroscopic properties similar to the native pigment in the dark-state. However, its photobleaching behavior is altered, showing a Meta I-like photoproduct. This behavior reflects a steric constraint imposed by the 7-methyl group that affects the conformational change in the binding pocket as a result of retinal photoisomerization. Transducin activation is reduced, when compared to the native pigment with 11-cis-retinal. Molecular dynamics simulations suggest coupling of the C7 methyl group and the beta-ionone ring with Met207 in transmembrane helix 5 in agreement with recent experimental results.
منابع مشابه
The role of the 11-cis-retinal ring methyl substituents in visual pigment formation.
Artificial visual pigment formation from ring-demethylated retinals was studied in an effort to understand the effect that methyl groups on the chromophore cyclohexenyl ring have on the visual cycle. The stereoselective synthesis of the 11-cis-ring-demethylated analogues involves thallium-accelerated Suzuki cross-coupling reactions and highly stereocontrolled Wittig reactions to form key bonds....
متن کامل6-s-cis Conformation and polar binding pocket of the retinal chromophore in the photoactivated state of rhodopsin.
The visual pigment rhodopsin is unique among the G protein-coupled receptors in having an 11-cis retinal chromophore covalently bound to the protein through a protonated Schiff base linkage. The chromophore locks the visual receptor in an inactive conformation through specific steric and electrostatic interactions. This efficient inverse agonist is rapidly converted to an agonist, the unprotona...
متن کاملThe C9 methyl group of retinal interacts with glycine-121 in rhodopsin.
The visual pigment rhodopsin is a prototypical G protein-coupled receptor. These receptors have seven transmembrane helices and are activated by specific receptor-ligand interactions. Rhodopsin is unusual in that its retinal prosthetic group serves as an antagonist in the dark in the 11-cis conformation but is rapidly converted to an agonist on photochemical cis to trans isomerization. Receptor...
متن کاملMechanism of rhodopsin activation as examined with ring-constrained retinal analogs and the crystal structure of the ground state protein.
The guanine nucleotide-binding protein (G-protein)-coupled receptor superfamily (GPCR) is comprised of a large group of membrane proteins involved in a wide range of physiological signaling processes. The functional switch from a quiescent to an active conformation is at the heart of GPCR action. The GPCR rhodopsin has been studied extensively because of its key role in scotopic vision. The gro...
متن کاملCoupling of retinal isomerization to the activation of rhodopsin.
Activation of the visual pigment rhodopsin is caused by 11-cis to -trans isomerization of its retinal chromophore. High-resolution solid-state NMR measurements on both rhodopsin and the metarhodopsin II intermediate show how retinal isomerization disrupts helix interactions that lock the receptor off in the dark. We made 2D dipolar-assisted rotational resonance NMR measurements between (13)C-la...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Vision Research
دوره 46 شماره
صفحات -
تاریخ انتشار 2006