THE LIGAND-BINDING DOMAIN IN METABOTROPIC GLUTAMATE RECEPTORS IS RELATED TO BACTERIAL PERIPLASMIC BINDING-PROTEINS

Receptors for the major excitatory neurotransmitter glutamate include metabotropic (G protein-coupled) and ionotropic (glutamate-gated ion c hannel) types. These receptors have large, presumably extracellular, a mino-terminal domains. Sensitive sequence analysis techniques indicate that the metabotropic receptor extracellular domain is similar to bac terial periplasmic amino acid binding proteins. A structural model bui lt using the observed similarity predicts a ligand-binding site, and m utants with conservative amino acid substitutions at this site are sho wn to have reduced ligand affinity. The metabotropic receptor extracel lular domain is a member of a family of structural domains linked to a variety of receptor types, including ionotropic glutamate receptors.