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The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region.


ABSTRACT: Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations. The hinge region is highly variable among iGluRs and fine-tunes gating activity, suggesting that in GluD2 this region has evolved to only respond to micromolar concentrations of D-serine.

SUBMITTER: Tapken D 

PROVIDER: S-EPMC5384001 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region.

Tapken Daniel D   Steffensen Thomas Bielefeldt TB   Leth Rasmus R   Kristensen Lise Baadsgaard LB   Gerbola Alexander A   Gajhede Michael M   Jørgensen Flemming Steen FS   Olsen Lars L   Kastrup Jette Sandholm JS  

Scientific reports 20170407


Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-bindin  ...[more]

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