A curvature-dependent membrane binding by tyrosine kinase Fer involves an intrinsically disordered region.
A curvature-dependent membrane binding by tyrosine kinase Fer involves an intrinsically disordered region.
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酪氨酸激酶 Fer 的曲率依赖性膜结合涉及本质上无序的区域。
DOI：
10.1016/j.bbrc.2017.12.009
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Yamamoto;H.;Kondo;A.;Itoh;T.
酪氨酸激酶是介导质膜信号转导的重要酶。虽然酪氨酸激酶的膜定位的意义已经得到了很好的评价，但膜曲率在其调节中的作用尚不清楚。在这里，我们证明了酪氨酸激酶Fer中的一个内在无序区域作为膜曲率传感器，在体外优先结合高度弯曲的膜。该区域与弯曲膜相互作用形成两亲性α-螺旋，疏水残基排列在螺旋结构的一侧。此外，酪氨酸激酶的活性被膜以依赖于曲率的方式显著增强。我们提出了一个基于分子内相互作用和由其内在无序区域介导的曲率依赖膜结合的铁调控模型。
Tyrosine kinases are important enzymes that mediate signal transduction at the plasma membrane. While the significance of membrane localization of tyrosine kinases has been well evaluated, the role of membrane curvature in their regulation is unknown. Here, we demonstrate that an intrinsically disordered region in the tyrosine kinase Fer acts as a membrane curvature sensor that preferentially binds to highly curved membranesin vitro. This region forms an amphipathic α-helix upon interaction with curved membranes, aligning hydrophobic residues on one side of the helical structure. Further, the tyrosine kinase activity of Fer is significantly enhanced by the membrane in a manner dependent on curvature. We propose a model for the regulation of Fer based on an intramolecular interaction and the curvature-dependent membrane binding mediated by its intrinsically disordered region.