Venkitaramani Deepa V, Fulton D Bruce, Andreotti Amy H, Johansen Kristen M, Johansen Jørgen
Department of Biochemistry, Biophysics, and Molecular Biology, 3156 Molecular Biology Building, Iowa State University Ames, IO 50011, USA.
Biochim Biophys Acta. 2006 Mar;1763(3):322-9. doi: 10.1016/j.bbamcr.2006.02.013. Epub 2006 Mar 24.
The EF-hand family of calcium-binding proteins regulates cellular signal transduction events via calcium-dependent interactions with target proteins. Here, we show that the COOH-terminal tail of the leech homolog of protein phosphatase 4 regulatory subunit 2 (PP4-R2) interacts with the small neuronal EF-hand calcium-binding protein, Calsensin, in a calcium-dependent manner. Using two-dimensional NMR spectroscopy and chemical shift perturbations we have identified and mapped the residues of Calsensin that form a binding surface for PP4-R2. We show that the binding groove is formed primarily of discontinuous hydrophobic residues located in helix 1, the hinge region, and helix 4 of the unicornate-type four helix structure of Calsensin. The findings suggest the possibility that calcium-dependent modulation of phosphatase complexes through interactions with small calcium-binding proteins may be a general mechanism for regulation of signal transduction pathways.
EF 手型钙结合蛋白家族通过与靶蛋白的钙依赖性相互作用来调节细胞信号转导事件。在此，我们表明蛋白磷酸酶 4 调节亚基 2（PP4-R2）的水蛭同源物的羧基末端尾巴以钙依赖性方式与小神经元 EF 手型钙结合蛋白 Calsensin 相互作用。利用二维核磁共振光谱和化学位移扰动，我们鉴定并绘制了 Calsensin 中形成与 PP4-R2 结合表面的残基。我们表明，结合凹槽主要由位于 Calsensin 单角型四螺旋结构的螺旋 1、铰链区和螺旋 4 中的不连续疏水残基形成。这些发现提示了一种可能性，即通过与小钙结合蛋白相互作用对磷酸酶复合物进行钙依赖性调节可能是调节信号转导途径的一种普遍机制。
