Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.

P. Paoletti (1) , F. Perin-Dureau (1) , A. Fayyazuddin (1) , A. Le Goff (1) , I. Callebaut (2) , J. Neyton (1)

1 NEURO - Laboratoire de Neurobiologie (UMR 8544)
2 LMCP - Laboratoire de minéralogie, cristallographie de Paris

Ionotropic glutamate receptors (iGluRs) bind agonists in a domain that has been crystallized and shown to have a bilobed structure. Eukaryotic iGluRs also possess a second extracellular N-terminal domain related to the bacterial periplasmic binding protein LIVBP. In NMDA receptors, the high-affinity Zn inhibition is eliminated by mutations in the LIVBP-like domain of the NR2A subunit. Using LIVBP structure, we have modeled this domain as two lobes connected by a hinge and show that six residues controlling Zn inhibition form two clusters facing each other across a central cleft. Upon Zn binding the two lobes close tightly around the divalent cation. Thus, the extracellular region of NR2A consists of a tandem of Venus flytrap domains, one binding the agonist and the other a modulatory ligand. Such a functional organization may apply to other eukaryotic iGluRs.

Domains: Neurons and Cognition [q-bio.NC]

P. Paoletti, F. Perin-Dureau, A. Fayyazuddin, A. Le Goff, I. Callebaut, et al.. Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.. Neuron, 2000, 28 (3), pp.911-25. ⟨hal-00139991⟩