Novel mechanism of functional regulation through myristoylation found on brain specific proteins.

我们最近利用质谱技术证明了从大鼠脑中分离的神经元特异性蛋白NAP22被肉豆蔻酰化，并利用一些物理化学方法证明了肉豆蔻酰化直接参与了它与钙调素的相互作用。此外，另一种肉豆蔻酰基化脑特异性蛋白（MARCKS）和HIV nef基因产物已被证明以同样的方式与钙调素相互作用。有趣的是，肉豆蔻酰基化蛋白的磷酸化消除了它们与钙调蛋白的相互作用。结构和功能研究表明，除了肉豆蔻酰化的必要条件外，这种相互作用还需要肉豆蔻酰化结构域的碱性氨基酸残基共存。目前，我们正在构建一种基于n -肉豆蔻酰基转移酶三级结构的预测肉豆蔻酰基化蛋白的算法，并提取那些被认为与钙调素相互作用的蛋白。阐明受肉豆蔻酰化作用调控的蛋白作为细胞内信号转导系统的串话点，将已知的信号通路相互连接起来，构建细胞内信号转导网络的新图谱。

We have recently demonstrated using mass spectrometry technique that NAP22, a neuron specific protein, isolated from rat brain is myristoylated, and using some physicochemical methods that the myristoylation is directly involved in its interaction with calmodulin. Furthermore, the other myristoylated brain specific protein (MARCKS) and HIV nef gene product have been shown to interact with calmodulin in the same way. Interestingly, phosphorylations of the myristoylated proteins abolish their interactions with calmodulin. The structural and functional studies have revealed that, besides the necessary conditions for myristoylation, the interaction requires co-existence of basic amino acid residue at the myristoylated domain. Now, we are constructing an algorithm to predict myristoylated proteins on the basis of tertiary structure of N-myristoyl transferase, and to extract those assumed to interact with calmodulin. Elucidating the proteins whose functions are regulated by the myristoylation as cross-talk points in the intracellular signal transduction system, the known signaling pathways will be linked with each other, and the novel map of the intracellular signal transduction network will be constructed.