A G protein-coupled receptor at work: the rhodopsin model.
G protein-coupled receptors (GPCRs) are ubiquitous signal transducers in cell membranes, as well as important drug targets. Interaction with extracellular agonists turns the seven transmembrane helix (7TM) scaffold of a GPCR into a catalyst for GDP and GTP exchange in heterotrimeric Galphabetagamma proteins. Activation of the model GPCR, rhodopsin, is triggered by photoisomerization of its retinal ligand. From the augmentation of biochemical and biophysical studies by recent high-resolution 3D structures, its activation intermediates can now be interpreted as the stepwise engagement of protein domains. Rearrangement of TM5-TM6 opens a crevice at the cytoplasmic side of the receptor into which the C terminus of the Galpha subunit can bind. The Galpha C-terminal helix is used as a transmission rod to the nucleotide binding site. The mechanism relies on dynamic interactions between conserved residues and could therefore be common to other GPCRs.
Hofmann
Klaus Peter
KP
Institut für Medizinische Physik und Biophysik (CC2), Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. klaus_peter.hofmann@charite.de
Scheerer
Patrick
P
Hildebrand
Peter W
PW
Choe
Hui-Woog
HW
Park
Jung Hee
JH
Heck
Martin
M
Ernst
Oliver P
OP
D000818:Animals; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin; D020962:Heterotrimeric GTP-Binding Proteins