Fyn酪氨酸激酶SH3结构域中疏水核心突变对内部动力学的响应。
The response of internal dynamics to hydrophobic core mutations in the SH3 domain from the Fyn tyrosine kinase.
作者信息
Mittermaier Anthony, Kay Lewis E
机构信息
Departments of Biochemistry, Chemistry and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
出版信息
Protein Sci. 2004 Apr;13(4):1088-99. doi: 10.1110/ps.03502504.
Abstract
We have used (15)N- and (2)H-NMR spin relaxation experiments to study the response of backbone and side-chain dynamics when a leucine or valine is substituted for a completely buried phenylalanine residue in the SH3 domain from the Fyn tyrosine kinase. Several residues show differences in the time scales and temperature dependences of internal motions when data for the three proteins are compared. Changes were also observed in the magnitude of dynamics, with the valine, and to a lesser extent leucine mutant, showing enhanced flexibility compared to the wild-type (WT) protein. The motions of many of the same amide and methyl groups are affected by both mutations, identifying a set of loci where dynamics are sensitive to interactions involving the targeted side chain. These results show that contacts within the hydrophobic core affect many aspects of internal mobility throughout the Fyn SH3 domain.
摘要
我们利用（15）N-和（2）H-NMR自旋弛豫实验，研究了在Fyn酪氨酸激酶的SH3结构域中，当亮氨酸或缬氨酸取代一个完全埋藏的苯丙氨酸残基时，主链和侧链动力学的响应。比较这三种蛋白质的数据时，几个残基在内部运动的时间尺度和温度依赖性上表现出差异。在动力学幅度上也观察到了变化，缬氨酸突变体以及程度稍轻的亮氨酸突变体，与野生型（WT）蛋白质相比，表现出增强的灵活性。许多相同的酰胺基和甲基的运动都受到这两种突变的影响，确定了一组动力学对涉及目标侧链的相互作用敏感的位点。这些结果表明，疏水核心内的接触会影响Fyn SH3结构域中内部流动性的许多方面。
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