Coupling of agonist binding to effector domain activation in metabotropic glutamate-like receptors.
Many membrane receptors are made of a ligand binding domain and an effector domain mediating intracellular signaling. This is the case for the metabotropic glutamate-like G-protein-coupled receptors. How ligand binding leads to the active conformation of the effector domain in such receptors is largely unknown. Here, we used an evolutionary trace analysis and mutagenesis to identify critical residues involved in the allosteric coupling between the Venus flytrap ligand binding domain (VFT) and the heptahelical G-protein activating domain of the metabotropic glutamate-like receptors. We have shown that a conserved interdomain disulfide bridge is required for this allosteric interaction. Taking into account that these receptors are homodimers, this finding provides important new information explaining how the different conformations of the dimer of VFT lead to different signaling of such dimeric receptors.
Rondard
Philippe
P
CNRS Unité Mixte de Recherche 5203, INSERM U661, Universités Montpellier 1 and 2, France.
Liu
Jianfeng
J
Huang
Siluo
S
Malhaire
Fanny
F
Vol
Claire
C
Pinault
Alexia
A
Labesse
Gilles
G
Pin
Jean-Philippe
JP
D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D018094:Receptors, Metabotropic Glutamate