6L6F

GluK3 receptor complex with UBP301

Summary for 6L6F

• Entry DOI: 10.2210/pdb6l6f/pdb
• EMDB information: 0839
• Descriptor: Glutamate receptor ionotropic, kainate 3 (1 entity in total)
• Functional Keywords: membrane protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 375939.69

Authors

Kumar, J.,Kumari, J.,Burada, A.P. (deposition date: 2019-10-28, release date: 2020-03-04, Last modification date: 2024-11-13)

Primary citation

Kumari, J.,Bendre, A.D.,Bhosale, S.,Vinnakota, R.,Burada, A.P.,Tria, G.,Ravelli, R.B.G.,Peters, P.J.,Joshi, M.,Kumar, J.
Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM.
Int.J.Biol.Macromol., 149:1051-1058, 2020

PubMed Abstract: 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 GluK3 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 GluK3 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.

PubMed: 32006583
DOI: 10.1016/j.ijbiomac.2020.01.282

Experimental method

ELECTRON MICROSCOPY (10.6 Å)