PDBsum entry 6mmt

Transport protein

PDB id: 6mmt

Contents

Protein chains

782 a.a.

772 a.a.

Ligands

NAG-NAG ×4

NAG ×29

PDB id:

6mmt

Name:

Transport protein

Title:

Triheteromeric nmda receptor glun1/glun2a/glun2a In the '1-knuckle' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at ph 7.4

Structure:

Glutamate receptor ionotropic, nmda 1. Chain: a, c. Fragment: unp residues 1-838. Synonym: glun1,glutamate [nmda] receptor subunit zeta-1,n-methyl-d- aspartate receptor subunit nr1,nmd-r1. Engineered: yes. Glutamate receptor ionotropic, nmda 2a. Chain: b. Fragment: unp residues 1-837.

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Variant: 1a. Gene: grin1, nmdar1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: tsa-201. Expression_system_organ: kidney.

Authors:

F.Jalali-Yazdi,S.Chowdhury,C.Yoshioka,E.Gouaux

Key ref:

F.Jalali-Yazdi et al. (2018). Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Cell, 175, 1520. PubMed id: 30500536 DOI: 10.1016/j.cell.2018.10.043

Date:

01-Oct-18 Release date: 28-Nov-18

Protein chains

P35439  (NMDZ1_RAT) -  Glutamate receptor ionotropic, NMDA 1 from Rattus norvegicus

Seq: 938 a.a.

Struc: 782 a.a.

Protein chains

Q00959  (NMDE1_RAT) -  Glutamate receptor ionotropic, NMDA 2A from Rattus norvegicus

Seq: 1464 a.a.

Struc: 772 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.cell.2018.10.043

Cell 175:1520 (2018)

PubMed id: 30500536

Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor.

F.Jalali-Yazdi, S.Chowdhury, C.Yoshioka, E.Gouaux.

ABSTRACT

N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate.