Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1
Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1
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DOI：
10.1016/j.str.2007.09.013
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发表时间：
2007-11-01
期刊：
影响因子：
5.7
通讯作者：
Sousa, Marcelo Carlos
中科院分区：
文献类型：
--
作者：
Stephen, Ricardo;Bereta, Grzegorz;Sousa, Marcelo Carlos
鸟苷环化酶激活蛋白(GCAPs)是一类位于N端的钙结合蛋白，调节光感受器细胞中的鸟苷环化酶，属于神经细胞钙感受器家族。许多NCS蛋白显示出一种类似于恢复素的“钙-肉豆蔻基开关”，当钙离子结合时，埋藏在蛋白质内部的无钙状态的肉豆蔻基团就会完全暴露出来。在这里，我们提出了一个2.0埃分辨率的肉豆蔻酰化的钙结合的GCAP1的晶体结构。酰基被埋在钙离子结合的GCAP1中。这与钙离子结合的恢复素形成鲜明对比，在恢复素中，肉豆蔻基团暴露在溶剂中。此外，我们提供了直接证据表明，GCAP1中的酰基仍然处于无钙状态，不会发生转换。C端螺旋上的明显扭结和肉豆蔻基的存在允许对GCAP1活性至关重要的序列元件的聚集。
Guanylate cyclase-activating proteins (GCAPs) are Ca2+-binding proteins myristoylated at the N terminus that regulate guanylate cyclases in photoreceptor cells and belong to the family of neuronal calcium sensors (NCS). Many NCS proteins display a recoverin-like "calcium-myristoyl switch" whereby the myristoyl group, buried inside the protein in the Ca2+-free state, becomes fully exposed upon Ca2+ binding. Here we present a 2.0 angstrom resolution crystal structure of myristoylated GCAP1 with Ca2+ bound. The acyl group is buried inside Ca2+-bound GCAP1. This is in sharp contrast to Ca2+-bound recoverin, where the myristoyl group is solvent exposed. Furthermore, we provide direct evidence that the acyl group in GCAP1 remains buried in the Ca2+-free state and does not undergo switching. A pronounced kink in the C-terminal helix and the presence of the myristoyl group allow clustering of sequence elements crucial for GCAP1 activity.