Partial agonism in a G Protein-coupled receptor: role of the retinal ring structure in rhodopsin activation.
The visual process in rod cells is initiated by absorption of a photon in the rhodopsin retinal chromophore and consequent retinal cis/trans-isomerization. The ring structure of retinal is thought to be needed to transmit the photonic energy into conformational changes culminating in the active metarhodopsin II (Meta II) intermediate. Here, we demonstrate that cis-acyclic retinals, lacking four carbon atoms of the ring, can activate rhodopsin. Detailed analysis of the activation pathway showed that, although the photoproduct pathway is more complex, Meta II formed with almost normal kinetics. However, lack of the ring structure resulted in a low amount of Meta II and a fast decay of activity. We conclude that the main role of the ring structure is to maintain the active state, thus specifying a mechanism of activation by a partial agonist of the G protein-coupled receptor rhodopsin.
Bartl
Franz J
FJ
Institut für Medizinische Physik und Biophysik, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany. franx.bartl@charite.de
Fritze
Olaf
O
Ritter
Eglof
E
Herrmann
Rolf
R
Kuksa
Vladimir
V
Palczewski
Krzysztof
K
Hofmann
Klaus Peter
KP
Ernst
Oliver P
OP
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D007536:Isomerism; D007700:Kinetics; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000502:physiology*; D012160:Retina / Q000502:physiology / Q000648:ultrastructure*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012172:Retinaldehyde / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D017299:Rod Opsins / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled; D017299:Rod Opsins; C013110:metarhodopsins; D012243:Rhodopsin; D012172:Retinaldehyde