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Structure paper

TitleStructural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery.
Journal, issue, pagesSci Rep, Vol. 9, Issue 1, Page 10254, Year 2019
Publish dateJul 16, 2019
AuthorsJyoti Kumari / Rajesh Vinnakota / Janesh Kumar /
PubMed AbstractGluK3-kainate receptors are atypical members of the iGluR family that reside at both the pre- and postsynapse and play a vital role in the regulation of synaptic transmission. For a better ...GluK3-kainate receptors are atypical members of the iGluR family that reside at both the pre- and postsynapse and play a vital role in the regulation of synaptic transmission. For a better understanding of structural changes that underlie receptor functions, GluK3 receptors were trapped in desensitized and resting/closed states and structures analyzed using single particle cryo-electron microscopy. While the desensitized GluK3 has domain organization as seen earlier for another kainate receptor-GluK2, antagonist bound GluK3 trapped a resting state with only two LBD domains in dimeric arrangement necessary for receptor activation. Using structures as a guide, we show that the N-linked glycans at the interface of GluK3 ATD and LBD likely mediate inter-domain interactions and attune receptor-gating properties. The mutational analysis also identified putative N-glycan interacting residues. Our results provide a molecular framework for understanding gating properties unique to GluK3 and exploring the role of N-linked glycosylation in their modulation.
External linksSci Rep / PubMed:31311973 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.832 - 7.6 Å
Structure data

9821

6jfy

EMDB-9821, PDB-6jfy:
GluK3 receptor trapped in Desensitized state
Method: EM (single particle) / Resolution: 7.4 Å

9822

6jfz

EMDB-9822, PDB-6jfz:
GluK3 receptor complex with UBP310
Method: EM (single particle) / Resolution: 7.6 Å

PDB-6jmv:
Crystal structure of the GluK3 ligand binding domain complex with SYM and zinc
Method: X-RAY DIFFRACTION / Resolution: 1.832 Å

Chemicals

ChemComp-SYM:
2S,4R-4-METHYLGLUTAMATE

ChemComp-CL:
Unknown entry / Chloride

ChemComp-ZN:
Unknown entry

ChemComp-GOL:
GLYCEROL / Glycerol

ChemComp-ACT:
ACETATE ION / Acetate

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / Glutamate receptor / Kainate / SYM / UBP310

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