5CMC

Mnemiopsis leidyi ML032222a iGluR LBD E423S mutant glycine complex

5CMC の概要

• エントリーDOI: 10.2210/pdb5cmc/pdb
• 関連するPDBエントリー: 4YKI 5CMB
• 分子名称: ML032222a iGluR, GLYCINE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: membrane protein, glutamate receptor, ion channel
• 由来する生物種: Mnemiopsis leidyi (sea walnut)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58109.55

構造登録者

Mayer, M.L.,Thomas, A. (登録日: 2015-07-16, 公開日: 2016-07-20, 最終更新日: 2024-10-23)

主引用文献

Yu, A.,Alberstein, R.,Thomas, A.,Zimmet, A.,Grey, R.,Mayer, M.L.,Lau, A.Y.
Molecular lock regulates binding of glycine to a primitive NMDA receptor.
Proc.Natl.Acad.Sci.USA, 113:E6786-E6795, 2016

PubMed Abstract: The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants.

PubMed: 27791085
DOI: 10.1073/pnas.1607010113

実験手法

X-RAY DIFFRACTION (1.28 Å)