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

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • srep46145

    Final published version, 1 MB, PDF-document

Daniel Tapken, Thomas Bielefeldt Steffensen, Rasmus Leth, Lise Baadsgaard Kristensen, Alexander Gerbola, Michael Gajhede, Flemming Steen Jørgensen, Lars Olsen, Jette Sandholm Kastrup

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.

Original languageEnglish
Article number46145
JournalScientific Reports
Volume7
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 7 Apr 2017

    Research areas

  • Journal Article

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 179671869