The ring of the rhodopsin chromophore in a hydrophobic activation switch within the binding pocket.
The current view that the beta-ionone ring of the rhodopsin chromophore vacates its binding pocket within the protein early in the photocascade has been adopted in efforts to provide structural models of photoreceptor activation. This event casts doubt on the ability of this covalently bonded ligand to participate directly in later stages involving activation of the photoreceptor and it is difficult to translate into predictions for the activation of related G protein-coupled receptors by diffusable ligands (e.g. neurotransmitters). The binding pocket fixes the formally equivalent pair of ring methyl groups (C16/C17) in different orientations that can be distinguished easily by (13)C NMR. Solid-state NMR observations on C16 and C17 are reported here that show instead that the ring is retained with strong selective interactions within the binding site into the activated state. We further show how increased steric interactions for this segment in the activated receptor can be explained by adjustment in the protein structure around the ring whilst it remains in its original location. This describes a plausible role for the ring in operating a hydrophobic switch from within the aromatic cluster of helix 6 of rhodopsin, which is coupled to electronic changes within the receptor through water-mediated, hydrogen-bonded networks between the conserved residues in G protein-coupled receptors.
The Biomembrane Structure Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. paul.spooner@bioch.ox.ac.uk
Paul J R
PJ
Spooner
Jonathan M
JM
Sharples
Scott C
SC
Goodall
Petra H M
PH
Bovee-Geurts
Michiel A
MA
Verhoeven
Johan
J
Lugtenburg
Arthur M A
AM
Pistorius
Willem J
WJ
Degrip
Anthony
A
Watts
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D045792:Norisoprenoids / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010786:Photoreceptor Cells / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D014785:Vision, Ocular
D045792:Norisoprenoids; D011510:Proteolipids; C020485:proteoliposomes; D012243:Rhodopsin; C008157:beta-ionone