4KCC

Crystal Structure of the NMDA Receptor GluN1 Ligand Binding Domain Apo State

Summary for 4KCC

• Entry DOI: 10.2210/pdb4kcc/pdb
• Related: 1PB7 1PB8 1PBQ 4KCD
• Descriptor: Glutamate receptor ionotropic, NMDA 1, PHOSPHATE ION (3 entities in total)
• Functional Keywords: membrane protein
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P35439
• Total number of polymer chains: 1
• Total formula weight: 33435.00

Authors

Berger, A.J.,Lau, A.Y.,Mayer, M.L. (deposition date: 2013-04-24, release date: 2013-07-31, Last modification date: 2023-09-20)

Primary citation

Yao, Y.,Belcher, J.,Berger, A.J.,Mayer, M.L.,Lau, A.Y.
Conformational Analysis of NMDA Receptor GluN1, GluN2, and GluN3 Ligand-Binding Domains Reveals Subtype-Specific Characteristics.
Structure, 21:1788-1799, 2013

PubMed Abstract: The NMDA receptor family of glutamate receptor ion channels is formed by obligate heteromeric assemblies of GluN1, GluN2, and GluN3 subunits. GluN1 and GluN3 bind glycine, whereas GluN2 binds glutamate. Crystal structures of the GluN1 and GluN3A ligand-binding domains (LBDs) in their apo states unexpectedly reveal open- and closed-cleft conformations, respectively, with water molecules filling the binding pockets. Computed conformational free energy landscapes for GluN1, GluN2A, and GluN3A LBDs reveal that the apo-state LBDs sample closed-cleft conformations, suggesting that their agonists bind via a conformational selection mechanism. By contrast, free energy landscapes for the AMPA receptor GluA2 LBD suggest binding of glutamate via an induced-fit mechanism. Principal component analysis reveals a rich spectrum of hinge bending, rocking, twisting, and sweeping motions that are different for the GluN1, GluN2A, GluN3A, and GluA2 LBDs. This variation highlights the structural complexity of signaling by glutamate receptor ion channels.

PubMed: 23972471
DOI: 10.1016/j.str.2013.07.011

Experimental method

X-RAY DIFFRACTION (1.894 Å)