Coupling 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-labels on the retinal chromophore and specific (13)C-labels on tyrosine, glycine, serine, and threonine in the retinal binding site of rhodopsin. The essential aspects of the isomerization trajectory are a large rotation of the C20 methyl group toward extracellular loop 2 and a 4- to 5-A translation of the retinal chromophore toward transmembrane helix 5. The retinal-protein contacts observed in the active metarhodopsin II intermediate suggest a general activation mechanism for class A G protein-coupled receptors involving coupled motion of transmembrane helices 5, 6, and 7.
Patel
Ashish B
AB
Department of Physiology and Biophysics, Center for Structural Biology, Stony Brook University, NY 11794-5215, USA.
Crocker
Evan
E
Eilers
Markus
M
Hirshfeld
Amiram
A
Sheves
Mordechai
M
Smith
Steven O
SO
D001665:Binding Sites; D007536:Isomerism; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D012172:Retinaldehyde / Q000737:chemistry*; D012243:Rhodopsin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism
C013110:metarhodopsins; D012243:Rhodopsin; D012172:Retinaldehyde