期刊
STRUCTURE
卷 21, 期 10, 页码 1788-1799出版社
CELL PRESS
DOI: 10.1016/j.str.2013.07.011
关键词
-
资金
- Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy [W-31-109-Eng-38]
- National Science Foundation [OCI-1053575]
- Intramural Research Program of the National Institute of Child Health and Human Development, NIH, Department of Health and Human Services
- NIH [GM094495]
- Barry Grant
The NMDA receptor family of glutamate receptor ion channels is formed by obligate heteromeric assemblies of GluN1, GluN2, and GluN3 subunits. GluN1 and GluN3 bind glycine, whereas GluN2 binds glutamate. Crystal structures of the GluN1 and GluN3A ligand-binding domains (LBDs) in their apo states unexpectedly reveal open- and closed-cleft conformations, respectively, with water molecules filling the binding pockets. Computed conformational free energy landscapes for GluN1, GluN2A, and GluN3A LBDs reveal that the apo-state LBDs sample closed-cleft conformations, suggesting that their agonists bind via a conformational selection mechanism. By contrast, free energy landscapes for the AMPA receptor GluA2 LBD suggest binding of glutamate via an induced-fit mechanism. Principal component analysis reveals a rich spectrum of hinge bending, rocking, twisting, and sweeping motions that are different for the GluN1, GluN2A, GluN3A, and GluA2 LBDs. This variation highlights the structural complexity of signaling by glutamate receptor ion channels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据