Homology model of the closed, functionally active, form of the amino terminal domain of mGluR1

The amino terminal domain (ATD) of metabotropic glutamate receptors (mGluRs ) contains the neurotransmitter binding site and is related in sequence to leucine/isoleucine/valine binding proteins (LIVBP). It has been proposed th at the ATD of mGluRs shares with periplasmic binding proteins a common mech anism of ligand binding and processing which involves the equilibrium betwe en closed and open Forms. The availability of the X-ray structure of LIVBP in its open, unliganded form. has allowed the construction of homology mode ls of the ATD of mGluR1 which have been instrumental in clarifying the mode of binding of agonists and antagonists. We propose in this paper the use o f the X-ray structure of AmiC. the controller of transcription antiterminat ion in thr amidase operon of Pseudomonas aeruginosa as suitable template fo r the construction of the closed form of the ATD of mGluR1. Thr resulting m odel of the closed form of the ATD of mGluR1 indicates that several interdo main hydrogen bonds and salt bridges may be Formed upon domain contraction and that the ligand directly participates to this interdomain network. (C) 2001 Published by Elsevier Science Ltd.