6mmr

From Proteopedia

Jump to: navigation, search

Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Symmetric' conformation, in complex with glycine and glutamate, in the presence of 1 millimolar zinc chloride, 3 millimolar EDTA, and at pH 7.4

Structural highlights

6mmr is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 5.13Å
Experimental data:Check to display Experimental Data
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NMDZ1_RAT NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. Plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors.[1]

Publication Abstract from PubMed

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.

Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor.,Jalali-Yazdi F, Chowdhury S, Yoshioka C, Gouaux E Cell. 2018 Nov 29;175(6):1520-1532.e15. doi: 10.1016/j.cell.2018.10.043. PMID:30500536[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
reviews cite this structure
-1 more
other articles
No citations found

See Also

References

  1. ↑ Inanobe A, Furukawa H, Gouaux E. Mechanism of partial agonist action at the NR1 subunit of NMDA receptors. Neuron. 2005 Jul 7;47(1):71-84. PMID:15996549 doi:10.1016/j.neuron.2005.05.022
  2. ↑ Jalali-Yazdi F, Chowdhury S, Yoshioka C, Gouaux E. Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Cell. 2018 Nov 29;175(6):1520-1532.e15. doi: 10.1016/j.cell.2018.10.043. PMID:30500536 doi:http://dx.doi.org/10.1016/j.cell.2018.10.043

Contents


6mmr, resolution 5.13Å

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6mmr"
Personal tools