4.8 Article

Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTS1)

期刊

CELL REPORTS
卷 42, 期 1, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2023.112015

关键词

-

向作者/读者索取更多资源

Nuclear magnetic resonance (NMR) studies have shown that fast methyl sidechain dynamics can provide information about entropically-driven allostery. This study focuses on the fast dynamics of a thermostabilized G protein-coupled receptor (GPCR), neurotensin receptor 1 (NTS1), using 13C epsilon-methionine chemical shift-based global order parameters. The results indicate the presence of substates with different lifetimes in the NTS1 solution ensemble, and the rapid fluctuations of individual methionine residues are correlated with ligand pharmacology, suggesting a role for sub-microsecond dynamics and conformational entropy in GPCR ligand discrimination.
Nuclear magnetic resonance (NMR) studies have revealed that fast methyl sidechain dynamics can report on entropically-driven allostery. Yet, NMR applications have been largely limited to the super-microsecond motional regimes of G protein-coupled receptors (GPCRs). We use 13C epsilon-methionine chemical shift-based global order parameters to test if ligands affect the fast dynamics of a thermostabilized GPCR, neurotensin receptor 1 (NTS1). We establish that the NTS1 solution ensemble includes substates with lifetimes on several, discrete timescales. The longest-lived states reflect those captured in agonist-and inverse agonist-bound crystal structures, separated by large energy barriers. We observe that the rapid fluctuations of individual methionine residues, superimposed on these long-lived states, respond collectively with the degree of fast, global dynamics correlating with ligand pharmacology. This approach lends confidence to interpreting spectra in terms of local structure and methyl dihedral angle geometry. The results suggest a role for sub -microsecond dynamics and conformational entropy in GPCR ligand discrimination.

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。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据