The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region
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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; Steffensen, Thomas Bielefeldt; Leth, Rasmus; Kristensen, Lise Baadsgaard; Gerbola, Alexander; Gajhede, Michael; Jørgensen, Flemming Steen; Olsen, Lars; Kastrup, Jette Sandholm.
In: Scientific Reports, Vol. 7, 46145, 07.04.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region
AU - Tapken, Daniel
AU - Steffensen, Thomas Bielefeldt
AU - Leth, Rasmus
AU - Kristensen, Lise Baadsgaard
AU - Gerbola, Alexander
AU - Gajhede, Michael
AU - Jørgensen, Flemming Steen
AU - Olsen, Lars
AU - Kastrup, Jette Sandholm
PY - 2017/4/7
Y1 - 2017/4/7
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/srep46145
DO - 10.1038/srep46145
M3 - Journal article
C2 - 28387240
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 46145
ER -
ID: 179671869