Determinants of endogenous ligand specificity divergence among metabotropic glutamate receptors.

ABSTRACT: To determine the structural origins of diverse ligand response specificities among metabotropic glutamate receptors (mGluRs), we combined computational approaches with mutagenesis and ligand response assays to identify specificity-determining residues in the group I receptor, mGluR1, and the group III receptors, mGluR4 and mGluR7. Among these, mGluR1 responds to L-glutamate effectively, whereas it binds weakly to another endogenous ligand, L-serine-O-phosphate (L-SOP), which antagonizes the effects of L-glutamate. In contrast, mGluR4 has in common with other group III mGluR that it is activated with higher potency and efficacy by L-SOP. mGluR7 differs from mGluR4 and other group III mGluR in that L-glutamate and L-SOP activate it with low potency and efficacy. Enhanced versions of the evol

SUBMITTER: Kang HJ 

PROVIDER: S-EPMC4317032 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature