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TitleCryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 1, Page 84-91, Year 2020
Publish dateJan 10, 2020
AuthorsAnanth Prasad Burada / Rajesh Vinnakota / Janesh Kumar /
PubMed AbstractIonotropic 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 ...Ionotropic 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.
External linksNat Struct Mol Biol / PubMed:31925409 / PubMed Central
MethodsEM (single particle)
Resolution8.1 Å
Structure data

0773

6ksp

EMDB-0773, PDB-6ksp:
Rat GluD1 receptor(splayed conformation) in complex with 7-CKA and Calcium ions
Method: EM (single particle) / Resolution: 8.1 Å

0774

6kss

EMDB-0774, PDB-6kss:
Rat GluD1 receptor(compact conformation) in complex with 7-CKA and Calcium ions
Method: EM (single particle) / Resolution: 8.1 Å

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / complex

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