Yamamoto Hikaru, Kondo Akihiro, Itoh Toshiki
Division of Membrane Biology, Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo, 657-8501, Japan.
Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):1522-1527. doi: 10.1016/j.bbrc.2017.12.009. Epub 2017 Dec 5.
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 membranes in 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.
酪氨酸激酶是介导质膜信号转导的重要酶。虽然酪氨酸激酶膜定位的重要性已得到充分评估，但其调控中膜曲率的作用尚不清楚。在这里，我们证明酪氨酸激酶Fer中一个内在无序区域充当膜曲率传感器，在体外优先结合高度弯曲的膜。该区域在与弯曲膜相互作用时形成两亲性α螺旋，使疏水残基排列在螺旋结构的一侧。此外，Fer的酪氨酸激酶活性以曲率依赖的方式被膜显著增强。我们基于分子内相互作用及其内在无序区域介导的曲率依赖的膜结合，提出了一种Fer的调控模型。
