Title | Structural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery [National Cryo-Electron Microscopy Facility] |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Kumari J, Vinnakota R, Kumar J |
Journal | Sci Rep |
Volume | 9 |
Issue | 1 |
Pagination | 10254 |
Date Published | 2019 Jul 16 |
ISSN | 2045-2322 |
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. |
DOI | 10.1038/s41598-019-46770-z |
Alternate Journal | Sci Rep |
PubMed ID | 31311973 |
PubMed Central ID | PMC6635489 |
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) / |
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