6kss | pdb_00006kss
Rat GluD1 receptor(compact conformation) in complex with 7-CKA and Calcium ions
Structural highlights
Function[GRID1_RAT] Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. Publication Abstract from PubMedIonotropic orphan delta (GluD) receptors are not gated by glutamate or any other endogenous ligand but are grouped with ionotropic glutamate receptors (iGluRs) based on sequence similarity. GluD1 receptors play critical roles in synaptogenesis and synapse maintenance and have been implicated in neuronal disorders, including schizophrenia, cognitive deficits, and cerebral ataxia. Here we report cryo-EM structures of the rat GluD1 receptor complexed with calcium and the ligand 7-chlorokynurenic acid (7-CKA), elucidating molecular architecture and principles of receptor assembly. The structures reveal a non-swapped architecture at the interface of the extracellular amino-terminal domain (ATD) and the ligand-binding domain (LBD). This finding is in contrast with structures of other families of iGluRs, where the dimer partners between the ATD and LBD layers are swapped. Our results demonstrate that principles of architecture and symmetry are not conserved between delta receptors and other iGluRs and provide a molecular blueprint for understanding the functions of the 'orphan' class of iGluRs. Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture.,Burada AP, Vinnakota R, Kumar J Nat Struct Mol Biol. 2020 Jan;27(1):84-91. doi: 10.1038/s41594-019-0359-y. Epub, 2020 Jan 10. PMID:31925409[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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