Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor

Naoki Kunishima, Yoshimi Shimada, Yuji Tsuji, Toshihiro Sato, Masaki Yamamoto, Takashi Kumasaka, Shigetada Nakanishi, Hisato Jingami () and Kosuke Morikawa ()
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Naoki Kunishima: Departments of Structural Biology
Yoshimi Shimada: Molecular Biology, Biomolecular Engineering Research Institute
Yuji Tsuji: Molecular Biology, Biomolecular Engineering Research Institute
Toshihiro Sato: Molecular Biology, Biomolecular Engineering Research Institute
Masaki Yamamoto: Structural Biophysics Laboratory, RIKEN Harima Institute
Takashi Kumasaka: Structural Biophysics Laboratory, RIKEN Harima Institute
Shigetada Nakanishi: Department of Biological Sciences Kyoto University Faculty of Medicine
Hisato Jingami: Molecular Biology, Biomolecular Engineering Research Institute
Kosuke Morikawa: Departments of Structural Biology

Nature, 2000, vol. 407, issue 6807, 971-977

Abstract: Abstract The metabotropic glutamate receptors (mGluRs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. Here we have determined three different crystal structures of the extracellular ligand-binding region of mGluR1—in a complex with glutamate and in two unliganded forms. They all showed disulphide-linked homodimers, whose ‘active’ and ‘resting’ conformations are modulated through the dimeric interface by a packed α-helical structure. The bi-lobed protomer architectures flexibly change their domain arrangements to form an ‘open’ or ‘closed’ conformation. The structures imply that glutamate binding stabilizes both the ‘active’ dimer and the ‘closed’ protomer in dynamic equilibrium. Movements of the four domains in the dimer are likely to affect the separation of the transmembrane and intracellular regions, and thereby activate the receptor. This scheme in the initial receptor activation could be applied generally to G-protein-coupled neurotransmitter receptors that possess extracellular ligand-binding sites.

Date: 2000
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DOI: 10.1038/35039564

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