期刊
MOLECULAR CELL
卷 81, 期 7, 页码 1384-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2021.02.002
关键词
-
资金
- NIH [R01 GM114130, R35-GM134962, R35-GM127303, R01-GM117923, R35-GM118105, F31NS093917]
Proteins are crucial in signal transduction and pharmacology, with G proteins playing a central role. Research has shown that a conserved network of amino acids dictates the release of G protein subunits, providing insights into the molecular basis of G protein activation.
(G) proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote guanosine triphosphate (GTP) binding and dissociation of G alpha from the G beta gamma subunits. Structural studies have revealed the molecular basis of subunit association with receptors, RGS proteins, and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We use cell signaling assays, molecular dynamics (MD) simulations, and biochemistry and structural analyses to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This G-R-E motif secures GTP and, through an allosteric link, discharges the G beta gamma dimer. Replacement of network residues prevents subunit dissociation regardless of agonist or GTP binding. These findings reveal the molecular basis of the final committed step of G protein activation.
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