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 journalJournal articleResearchpeer-review

Harvard

Tapken, D, Steffensen, TB, Leth, R, Kristensen, LB, Gerbola, A, Gajhede, M, Jørgensen, FS, Olsen, L & Kastrup, JS 2017, 'The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region', Scientific Reports, vol. 7, 46145. https://doi.org/10.1038/srep46145

APA

Tapken, D., Steffensen, T. B., Leth, R., Kristensen, L. B., Gerbola, A., Gajhede, M., ... Kastrup, J. S. (2017). The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region. Scientific Reports, 7, [46145]. https://doi.org/10.1038/srep46145

Vancouver

Tapken D, Steffensen TB, Leth R, Kristensen LB, Gerbola A, Gajhede M et al. The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region. Scientific Reports. 2017 Apr 7;7. 46145. https://doi.org/10.1038/srep46145

Author

Tapken, Daniel ; Steffensen, Thomas Bielefeldt ; Leth, Rasmus ; Kristensen, Lise Baadsgaard ; Gerbola, Alexander ; Gajhede, Michael ; Jørgensen, Flemming Steen ; Olsen, Lars ; Kastrup, Jette Sandholm. / The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region. In: Scientific Reports. 2017 ; Vol. 7.

Bibtex

@article{db7d5fcfc4e44eba8a99535264a3a912,
title = "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.",
keywords = "Journal Article",
author = "Daniel Tapken and Steffensen, {Thomas Bielefeldt} and Rasmus Leth and Kristensen, {Lise Baadsgaard} and Alexander Gerbola and Michael Gajhede and J{\o}rgensen, {Flemming Steen} and Lars Olsen and Kastrup, {Jette Sandholm}",
year = "2017",
month = "4",
day = "7",
doi = "10.1038/srep46145",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

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