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

在大脑特定蛋白质上发现通过肉豆蔻酰化进行功能调节的新机制。

• 批准号: 15590256
• 负责人: HAYASHI Nobuhiro
• 金额: $ 1.98万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590256/
• 关键词: myristoylation; calmodulin; intracellular signaling; molecular mechanism of brain; protein-protein interaction; target recognition mechanism; bioinformatics; molecular biology; バイオインフマティックス; バイオインフォマティックス

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.

我们最近利用质谱学技术证明了从大鼠脑中分离的神经元特异性蛋白NAP22是肉豆蔻酰化的，并用一些物理化学方法证明了肉豆蔻酸化直接参与了它与钙调蛋白的相互作用。此外，另一种肉豆蔻酰化的脑特异性蛋白(MARCKS)和HIV nef基因产物已被证明以同样的方式与钙调蛋白相互作用。有趣的是，肉豆蔻酰化蛋白的磷酸化取消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在肉豆蔻酸化的区域共存碱性氨基酸残基。现在，我们正在构建一种基于N-肉豆蔻酰基转移酶的三级结构来预测肉豆蔻酰化蛋白质的算法，并提取那些假定与钙调蛋白相互作用的蛋白质。阐明其功能受肉豆蔻酰化调控的蛋白质作为细胞内信号转导系统中的串通点，可以将已知的信号转导通路联系起来，构建新的细胞内信号转导网络图谱。

项目成果

Direct involvement of protein myristoylation in MARCKS-calmodulin interaction.

蛋白质肉豆蔻酰化直接参与 MARCKS-钙调蛋白相互作用。

• 发表时间: 2003
• 期刊: J.Biol.Chem. 278
• 作者: Matsubara;M.;et al.
• 通讯作者: et al.

Myristoylation-regulated direct interaction between calcium-bound calmodulin and N-terminal region of pp60v-src

• DOI: 10.1016/j.jmb.2004.02.041
• 发表时间: 2004-04-16
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Hayashi, N;Nakagawa, C;Matsushima, N
• 通讯作者: Matsushima, N

MYRbase : EvOluation of genome-wide glycine myristoylation enlarges functional spectrum of eukaryotic myristoylated proteins

MYRbase：全基因组甘氨酸肉豆蔻酰化的进化扩大了真核肉豆蔻酰化蛋白质的功能谱

• 发表时间: 2004
• 期刊: Genome Biology 5
• 作者: Sebastian Maurer-Stroh;et al.
• 通讯作者: et al.

Sebastian Maurer-Stroh, Masaki Gouda, Maria Novatchkova, Alexander Schleiffer, Georg, Schneider, Fernanda L.Sirota, Michael Wildpaner, Nobuhiro Hayashi, Frank Eisenhaber: "MYRbase : Evoluation of genome-wide glycine myristoylation enlarges functional spec

Sebastian Maurer-Stroh、Masaki Gouda、Maria Novatchkova、Alexander Schleiffer、Georg、Schneider、Fernanda L.Sirota、Michael Wildpaner、Nobuhiro Hayashi、Frank Eisenhaber：“MYRbase：全基因组甘氨酸肉豆蔻酰化的进化扩大了功能规格

Molecular mechanism for pterin-mediated inactivation of tyrosine hydroxylase: formation of insoluble aggregates of tyrosine hydroxylase.

蝶呤介导的酪氨酸羟化酶失活的分子机制：酪氨酸羟化酶不溶性聚集体的形成。

• DOI: 10.1093/jb/mvj073
• 发表时间: 2006
• 期刊: Journal of biochemistry
• 影响因子: 2.7
• 作者: Urano,Fumi;Hayashi,Nobuhiro;Arisaka,Fumio;Kurita,Hideki;Murata,Shizuaki;Ichinose,Hiroshi
• 通讯作者: Ichinose,Hiroshi