Dimer-based model for heptaspanning membrane receptors.
The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.
Franco
Rafael
R
Department Bioquímica i Biologia Molecular, Universitat de Barcelona, A. Diagonal, 645. 08028 Barcelona, Spain.
Casadó
Vicent
V
Mallol
Josefa
J
Ferré
Sergi
S
Fuxe
Kjell
K
Cortés
Antonio
A
Ciruela
Francisco
F
Lluis
Carmen
C
Canela
Enric I
EI
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D011956:Receptors, Cell Surface