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Closed state of both binding domains of homodimeric mGlu receptors is required for full activity
Kniazeff J, Bessis A-S, Maurel D, Ansanay H, Prezeau L and Pin J-P
Institut of Functional Genomics (IGF), Montpellier, France
Nat Struct Mol Biol. 2004;11(8):706-13.
Membrane receptors, which are key components in signal transduction, often function as dimers. These include some G protein-coupled receptors such as metabotropic glutamate (mGlu) receptors that possess large extracellular domains (ECDs) where agonists bind. How agonist binding in dimeric ECDs activates the effector domains remains largely unknown. The structure of the dimeric ECDs of mGlu1 solved in the presence of agonist revealed two specific conformations in which either one or both protomers are in an agonist-stabilized closed form. Here we examined whether both conformations correspond to an active form of the full-length receptor. Using a system that allows the formation of dimers made of a wildtype and a mutant subunit, we show that the closure of one ECD per dimer is sufficient to activate the receptor, but the closure of both ECDs is required for full activity.