Title : Structures of the extracellular
regions of the group
II /
III metabotropic glutamate
receptors
Abstract :
- Metabotropic glutamate receptors play major roles in the activation of excitatory synapses in the central nerve system
- We determined the crystal structure of the entire extracellular region of the group II receptor and that of the ligand-binding region of the group III receptor
- A comparison among groups I, II , and III provides the structural basis that could account for the discrimination of group-specific agonists
- Furthermore, the structure of group II includes the cysteine-rich domain , which is tightly linked to the ligand-binding domain by a disulfide bridge, suggesting a potential role in transmitting a ligand-induced conformational change into the downstream transmembrane region
- The structure also reveals the lateral interaction between the two cysteine-rich domains , which could stimulate clustering of the dimeric receptors on the cell surface
- We propose a general activation mechanism of the dimeric receptor coupled with both ligand-binding and interprotomer rearrangements