3u94

From Proteopedia

Crystal structure of the GluK3 ligand binding domain complex with glutamate and zinc: P21212 form

Structural highlights

3u94 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:	X-ray diffraction, Resolution 1.962Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRIK3_RAT Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.^[1]

Publication Abstract from PubMed

Kainate receptors (KARs) play a key role in the regulation of synaptic networks. Here, we show that zinc, a cation released at a subset of glutamatergic synapses, potentiates glutamate currents mediated by homomeric and heteromeric KARs containing GluK3 at 10-100 muM concentrations, whereas it inhibits other KAR subtypes. Potentiation of GluK3 currents is mainly due to reduced desensitization, as shown by kinetic analysis and desensitization mutants. Crystallographic and mutation analyses revealed that a specific zinc binding site is formed at the base of the ligand binding domain (LBD) dimer interface by a GluK3-specific aspartate (Asp759), together with two conserved residues, His762 and Asp730, the latter located on the partner subunit. In addition, we propose that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer interface, slows desensitization, and potentiates currents, providing a mechanism for KAR potentiation at glutamatergic synapses.

Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface.,Veran J, Kumar J, Pinheiro PS, Athane A, Mayer ML, Perrais D, Mulle C Neuron. 2012 Nov 8;76(3):565-78. doi: 10.1016/j.neuron.2012.08.027. PMID:23141068^[2]

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

References

↑ Venskutonyte R, Frydenvang K, Gajhede M, Bunch L, Pickering DS, Kastrup JS. Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate. J Struct Biol. 2011 Sep 1. PMID:21907808 doi:10.1016/j.jsb.2011.08.014
↑ Veran J, Kumar J, Pinheiro PS, Athane A, Mayer ML, Perrais D, Mulle C. Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface. Neuron. 2012 Nov 8;76(3):565-78. doi: 10.1016/j.neuron.2012.08.027. PMID:23141068 doi:http://dx.doi.org/10.1016/j.neuron.2012.08.027