5TPW

Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2A in complex with zinc at the GluN2A

5TPW の概要

• エントリーDOI: 10.2210/pdb5tpw/pdb
• 関連するPDBエントリー: 5TPZ 5TQ0 5TQ2
• 分子名称: NMDA glutamate receptor subunit, Glutamate receptor ionotropic, NMDA 2A, FAB, HEAVY CHAIN, ... (9 entities in total)
• 機能のキーワード: ion channel, nmda receptor, allosteric modulation, zinc inhibition, transport protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132949.11

構造登録者

Romero-Hernandez, A.,Simorowski, N.,Karakas, E.,Furukawa, H. (登録日: 2016-10-21, 公開日: 2016-12-14, 最終更新日: 2024-10-23)

主引用文献

Romero-Hernandez, A.,Simorowski, N.,Karakas, E.,Furukawa, H.
Molecular Basis for Subtype Specificity and High-Affinity Zinc Inhibition in the GluN1-GluN2A NMDA Receptor Amino-Terminal Domain.
Neuron, 92:1324-1336, 2016

PubMed Abstract: Zinc is vastly present in the mammalian brain and controls functions of various cell surface receptors to regulate neurotransmission. A distinctive characteristic of N-methyl-D-aspartate (NMDA) receptors containing a GluN2A subunit is that their ion channel activity is allosterically inhibited by a nano-molar concentration of zinc that binds to an extracellular domain called an amino-terminal domain (ATD). Despite physiological importance, the molecular mechanism underlying the high-affinity zinc inhibition has been incomplete because of the lack of a GluN2A ATD structure. Here we show the first crystal structures of the heterodimeric GluN1-GluN2A ATD, which provide the complete map of the high-affinity zinc-binding site and reveal distinctive features from the ATD of the GluN1-GluN2B subtype. Perturbation of hydrogen bond networks at the hinge of the GluN2A bi-lobe structure affects both zinc inhibition and open probability, supporting the general model in which the bi-lobe motion in ATD regulates the channel activity in NMDA receptors.

PubMed: 27916457
DOI: 10.1016/j.neuron.2016.11.006

実験手法

X-RAY DIFFRACTION (2.909 Å)