Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM
| Autor: | Sumedha Bhosale, Giancarlo Tria, Peter J. Peters, Janesh Kumar, Raimond B. G. Ravelli, Ameya D. Bendre, Manali Joshi, Ananth Prasad Burada, Jyoti Kumari, Rajesh Vinnakota |
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| Přispěvatelé: | RS: M4I - Nanoscopy, Institute of Nanoscopy (IoN) |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Agonist GLUTAMATE-RECEPTOR medicine.drug_class Kainate receptor 02 engineering and technology AMPA receptor Ligands Biochemistry Neurotransmitter binding 03 medical and health sciences Protein Domains Receptors Kainic Acid Structural Biology GLUK3 AMPA IMPLEMENTATION medicine Humans Receptor Molecular Biology 030304 developmental biology Hippocampal mossy fiber Aspartic Acid Neurotransmitter Agents 0303 health sciences Kainic Acid Chemistry Cryoelectron Microscopy Glutamate receptor Kainate General Medicine 021001 nanoscience & nanotechnology HEK293 Cells Structural biology GLUR7 Biophysics Ionotropic glutamate receptor Protein Multimerization Cryo-electron microscopy 0210 nano-technology |
| Zdroj: | International Journal of Biological Macromolecules, 149, 1051-1058. Elsevier |
| ISSN: | 0141-8130 |
| Popis: | Kainate receptors belong to the ionotropic glutamate receptor family and play critical roles in the regulation of synaptic networks. The kainate receptor subunit GluK3 has unique functional properties and contributes to presynaptic facilitation at the hippocampal mossy fiber synapses along with roles at the post-synapses. To gain structural insights into the unique functional properties and dynamics of GluK3 receptor, we imaged them via electron microscopy in the apo-state and in complex with either agonist kainate or antagonist UBP301. Our analysis of all the GIuK3 full-length structures not only provides insights into the receptor transitions between desensitized and closed states but also reveals a "non-classical" conformation of neurotransmitter binding domain in the closed-state distinct from that observed in AMPA and other kainate receptor structures. We show by molecular dynamics simulations that Asp759 influences the stability of the LBD dimers and hence could be responsible for the observed conformational variability and dynamics of the GIuK3 via electron microscopy. Lower dimer stability could explain faster desensitization and low agonist sensitivity of GluK3. In overview, our work helps to associate biochemistry and physiology of GluK3 receptors with their structural biology and offers structural insights into the unique functional properties of these atypical receptors. (C) 2020 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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