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 channel) types. These receptors have large, presumably extracellular, amino-terminal domains. Sensitive sequence analysis techniques indicate that the metabotropic receptor extracellular domain is similar to bacterial periplasmic amino acid binding proteins. A structural model built using the observed similarity predicts a ligand-binding site, and mutants with conservative amino acid substitutions at this site are shown to have reduced ligand affinity. The metabotropic receptor extracellular domain is a member of a family of structural domains linked to a variety of receptor types, including ionotropic glutamate receptors.
O'Hara
P J
PJ
ZymoGenetics, Inc., Seattle, Washington 98105.
Sheppard
P O
PO
Thøgersen
H
H
Venezia
D
D
Haldeman
B A
BA
McGrane
V
V
Houamed
K M
KM
Thomsen
C
C
Gilbert
T L
TL
Mulvihill
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016208:Databases, Factual; D005544:Forecasting; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D002352:Carrier Proteins; D008024:Ligands; D017470:Receptors, Glutamate