Glycine substitution in SH3-SH2 connector of Hck tyrosine kinase causes population shift from assembled to disassembled state.
Glycine substitution in SH3-SH2 connector of Hck tyrosine kinase causes population shift from assembled to disassembled state.
复制标题
Hck 酪氨酸激酶的 SH3-SH2 连接器中的甘氨酸取代导致群体从组装状态转变为分解状态。
DOI：
10.1016/j.bbagen.2020.129604
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Roux,Benoît
中科院分区：
文献类型：
--
作者：
Huang,Lei;Wright,Michelle;Yang,Sichun;Blachowicz,Lydia;Makowski,Lee;Roux,Benoît
A combination of small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations based on a coarse grained model is used to examine the effect of glycine substitutions in the short connector between the SH3 and SH2 domains of Hck, a member of the Src-family kinases. It has been shown previously that the activity of cSrc kinase is upregulated by substitution of 3 residues by glycine in the SH3-SH2 connector. Here, analysis of SAXS data indicates that the population of Hck in the disassembled state increases from 25% in the wild type kinase to 76% in the glycine mutant. This is consistent with the results of free energy perturbation calculations showing that the mutation in the connector shifts the equilibrium from the assembled to the disassembled state. This study supports the notion that the SH3-SH2 connector helps to regulate the activity of tyrosine kinases by shifting the population of the active state of the multidomain protein independent of C-terminal phosphorylation.
