Crystal structure of a myristoylated CAP-23/NAP-22 N-terminal domain complexed with Ca2+/calmodulin
Crystal structure of a myristoylated CAP-23/NAP-22 N-terminal domain complexed with Ca2+/calmodulin
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DOI：
10.1038/sj.emboj.7600093
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发表时间：
2004-02-25
期刊：
影响因子：
11.4
通讯作者：
Taniguchi, H
中科院分区：
文献类型：
--
作者：
Matsubara, M;Nakatsu, T;Taniguchi, H
已知多种病毒和信号转导蛋白是豆蔻酰化的。虽然豆蔻酰化在蛋白质-脂质相互作用中的作用已经很好地建立，但豆蔻酰化在蛋白质-蛋白质相互作用中的参与还不太清楚。CAP-23/NAP-22是参与轴突再生的脑特异性蛋白激酶C底物蛋白。尽管该蛋白缺乏任何典型的钙调蛋白（CaM）结合结构域，但它以高亲和力结合CaM。CAP-23/NAP-22与CaM的结合是肉豆蔻酰化依赖性的，并且N-末端肉豆蔻酰基团直接参与蛋白质-蛋白质相互作用。在这里，我们显示的晶体结构的钙离子-钙调素结合到豆蔻酰化的肽对应的N-末端结构域的CAP-23/NAP-22。肽的肉豆蔻酰基部分通过由CaM的N-和C-末端结构域中的疏水口袋产生的疏水隧道。除了肉豆蔻酰基外，肽中的几个氨基酸残基对CaM结合也很重要。这是一种新的结合模式，与其他CaM-靶复合物的结合机制非常不同。
A variety of viral and signal transduction proteins are known to be myristoylated. Although the role of myristoylation in protein-lipid interaction is well established, the involvement of myristoylation in protein-protein interactions is less well understood. CAP-23/NAP-22 is a brain-specific protein kinase C substrate protein that is involved in axon regeneration. Although the protein lacks any canonical calmodulin (CaM)-binding domain, it binds CaM with high affinity. The binding of CAP-23/NAP-22 to CaM is myristoylation dependent and the N-terminal myristoyl group is directly involved in the protein-protein interaction. Here we show the crystal structure of Ca2+-CaM bound to a myristoylated peptide corresponding to the N-terminal domain of CAP-23/NAP-22. The myristoyl moiety of the peptide goes through a hydrophobic tunnel created by the hydrophobic pockets in the N- and C-terminal domains of CaM. In addition to the myristoyl group, several amino-acid residues in the peptide are important for CaM binding. This is a novel mode of binding and is very different from the mechanism of binding in other CaM-target complexes.