5CMK

Crystal structure of the GluK2EM LBD dimer assembly complex with glutamate and LY466195

5CMK の概要

• エントリーDOI: 10.2210/pdb5cmk/pdb
• 関連するPDBエントリー: 2QS4 3G3F 4UQQ 5CMM
• 分子名称: Glutamate receptor ionotropic, kainate 2, GLUTAMIC ACID, LITHIUM ION, ... (7 entities in total)
• 機能のキーワード: membrane protein, transport protein
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : P42260
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59483.65

構造登録者

Chittori, S.,Mayer, M.L. (登録日: 2015-07-16, 公開日: 2016-07-20, 最終更新日: 2023-09-27)

主引用文献

Meyerson, J.R.,Chittori, S.,Merk, A.,Rao, P.,Han, T.H.,Serpe, M.,Mayer, M.L.,Subramaniam, S.
Structural basis of kainate subtype glutamate receptor desensitization.
Nature, 537:567-571, 2016

PubMed Abstract: Glutamate receptors are ligand-gated tetrameric ion channels that mediate synaptic transmission in the central nervous system. They are instrumental in vertebrate cognition and their dysfunction underlies diverse diseases. In both the resting and desensitized states of AMPA and kainate receptor subtypes, the ion channels are closed, whereas the ligand-binding domains, which are physically coupled to the channels, adopt markedly different conformations. Without an atomic model for the desensitized state, it is not possible to address a central problem in receptor gating: how the resting and desensitized receptor states both display closed ion channels, although they have major differences in the quaternary structure of the ligand-binding domain. Here, by determining the structure of the kainate receptor GluK2 subtype in its desensitized state by cryo-electron microscopy (cryo-EM) at 3.8 Å resolution, we show that desensitization is characterized by the establishment of a ring-like structure in the ligand-binding domain layer of the receptor. Formation of this 'desensitization ring' is mediated by staggered helix contacts between adjacent subunits, which leads to a pseudo-four-fold symmetric arrangement of the ligand-binding domains, illustrating subtle changes in symmetry that are important for the gating mechanism. Disruption of the desensitization ring is probably the key switch that enables restoration of the receptor to its resting state, thereby completing the gating cycle.

PubMed: 27580033
DOI: 10.1038/nature19352

実験手法

X-RAY DIFFRACTION (1.801 Å)