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Structural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery [National Cryo-Electron Microscopy Facility]

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TitleStructural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery [National Cryo-Electron Microscopy Facility]
Publication TypeJournal Article
Year of Publication2019
AuthorsKumari J, Vinnakota R, Kumar J
JournalSci Rep
Volume9
Issue1
Pagination10254
Date Published2019 Jul 16
ISSN2045-2322
Abstract

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.

DOI10.1038/s41598-019-46770-z
Alternate JournalSci Rep
PubMed ID31311973
PubMed Central IDPMC6635489
Grant List / / Wellcome Trust / United Kingdom
IA/I/13/2/501023 / / DBT India Alliance (Wellcome Trust/DBT India Alliance) /
BT/PR15450/COE/34/46/2016 / / Department of Biotechnology, Ministry of Science and Technology (DBT) /