Research Projects

Delta glutamate receptor ion channels are part of the ionotropic glutamate receptors (iGluRs) superfamily, essential for synaptogenesis and synaptic plasticity. They have been linked to neurological disorders like schizophrenia, autism spectrum disorder, cerebellar ataxia, intellectual disability, paraplegia, and retinal dystrophy. Delta receptors, GluD1 and GluD2, share a similar structure to other iGluRs, consisting of four subunits forming a tetramer. However, GluD1 and GluD2 receptors have a unique architecture, with no domain swapping between the ATD and LBD domains. This distinct architecture contributes to enhanced conformational flexibility in their extracellular domains. To address this knowledge gap, researchers are proposing stabilizing the extracellular domains of GluD receptors through protein engineering or chemical cross-linking. They will then determine GluD structures while trapped in apo, closed, and desensitized states using cryogenic electron microscopy (Cryo-EM), providing the first high-resolution insights into the gating mechanisms of GluD receptors. This approach will provide the first high-resolution insights into the gating mechanisms of GluD receptors.