1ISS

Crystal Structure of Metabotropic Glutamate Receptor Subtype 1 Complexed with an antagonist

Summary for 1ISS

• Entry DOI: 10.2210/pdb1iss/pdb
• Related: 1EWK 1EWT 1EWV 1ISR
• Descriptor: Metabotropic Glutamate Receptor subtype 1, (S)-(ALPHA)-METHYL-4-CARBOXYPHENYLGLYCINE (2 entities in total)
• Functional Keywords: signal transduction, neurotransmitter, g protein coupled receptor, antagonist, 4-carboxyphenylglycine, signaling protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell membrane; Multi-pass membrane protein: P23385
• Total number of polymer chains: 2
• Total formula weight: 110935.81

Authors

Tsuchiya, D.,Kunishima, N.,Kamiya, N.,Jingami, H.,Morikawa, K. (deposition date: 2001-12-21, release date: 2002-03-13, Last modification date: 2024-10-30)

Primary citation

Tsuchiya, D.,Kunishima, N.,Kamiya, N.,Jingami, H.,Morikawa, K.
Structural views of the ligand-binding cores of a metabotropic glutamate receptor complexed with an antagonist and both glutamate and Gd3+.
Proc.Natl.Acad.Sci.USA, 99:2660-2665, 2002

PubMed Abstract: Crystal structures of the extracellular ligand-binding region of the metabotropic glutamate receptor, complexed with an antagonist, (S)-(alpha)-methyl-4-carboxyphenylglycine, and with both glutamate and Gd3+ ion, have been determined by x-ray crystallographic analyses. The structure of the complex with the antagonist is similar to that of the unliganded resting dimer. The antagonist wedges the protomer to maintain an inactive open form. The glutamate/Gd3+ complex is an exact 2-fold symmetric dimer, where each bi-lobed protomer adopts the closed conformation. The surface of the C-terminal domain contains an acidic patch, whose negative charges are alleviated by the metal cation to stabilize the active dimeric structure. The structural comparison between the active and resting dimers suggests that glutamate binding tends to induce domain closing and a small shift of a helix in the dimer interface. Furthermore, an interprotomer contact including the acidic patch inhibited dimer formation by the two open protomers in the active state. These findings provide a structural basis to describe the link between ligand binding and the dimer interface.

PubMed: 11867751
DOI: 10.1073/pnas.052708599

Experimental method

X-RAY DIFFRACTION (3.3 Å)