Title : Structural basis of glutamate recognition by a dimeric metabotropic glutamate
receptor
Abstract :
- The metabotropic glutamate receptors ( mGluRs ) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system
- Here we have determined three different crystal structures of the extracellular ligand-binding region of mGluR1--in a complex with glutamate and in two unliganded forms
- They all showed disulphide-linked homodimers , whose 'active' and 'resting' conformations are modulated through the dimeric interface by a packed alpha-helical structure
- The bi-lobed protomer architectures flexibly change their domain arrangements to form an 'open' or 'closed' conformation
- The structures imply that glutamate binding stabilizes both the 'active' dimer and the 'closed' protomer in dynamic equilibrium
- Movements of the four domains in the dimer are likely to affect the separation of the transmembrane and intracellular regions , and thereby activate the receptor
- This scheme in the initial receptor activation could be applied generally to G-protein-coupled neurotransmitter receptors that possess extracellular ligand-binding sites