6L6F

GluK3 receptor complex with UBP301

6L6F の概要

• エントリーDOI: 10.2210/pdb6l6f/pdb
• EMDBエントリー: 0839
• 分子名称: Glutamate receptor ionotropic, kainate 3 (1 entity in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 375939.69

構造登録者

Kumar, J.,Kumari, J.,Burada, A.P. (登録日: 2019-10-28, 公開日: 2020-03-04, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (10.6 Å)