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首页> 外文期刊>Biochemistry >Liaison between Myristoylation and Cryptic EF-Hand Motif Confers Ca2+ Sensitivity to Neuronal Calcium Sensor-1
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Liaison between Myristoylation and Cryptic EF-Hand Motif Confers Ca2+ Sensitivity to Neuronal Calcium Sensor-1

机译：肉豆蔻酰化与隐性EF手基序之间的联系赋予Ca2 +对神经元钙传感器1的敏感性。

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摘要

Many members of the neuronal calcium sensor (NCS) protein family have a striking coexistence of two characteristics, that is, N-myristoylation and the cryptic EF-1 motif. We investigated the rationale behind this correlation in neuronal calcium sensor-1 (NCS-1) by restoring Ca2+ binding ability of the disabled EF-1 loop by appropriate mutations. The concurrence of canonical EF-1 and N-myristoylation considerably decreased the overall Ca2+ affinity, conformational flexibility, and functional activation of downstream effecter molecules (i.e., PI4K beta). Of a particular note, Ca2+ induced conformational change (which is the first premise for a CaBP to be considered as sensor) is considerably reduced in myristoylated proteins in which Ca2+-binding to EF-1 is restored. Moreover, Ca2+, which otherwise augments the enzymatic activity of PI4K beta (modulated by NCS-1), leads to a further decline in the modulated PI4K beta activity by myristoylated mutants (with canonical EF-1) pointing toward a loss of Ca2+ signaling and specificity at the structural as well as functional levels. This study establishes the presence of the strong liaison between myristoylation and cryptic EF-1 in NCS-1. Breaking this liaison results in the failure of Ca2+ specific signal transduction to downstream effecter molecules despite Ca2+ binding. Thus, the EF-1 disability is a prerequisite in order to append myristoylation signaling while preserving structural robustness and Ca2+ sensitivity/specificity in NCS-1.
机译：神经元钙传感器（NCS）蛋白家族的许多成员具有两个特征的显着共存，即N-肉豆蔻酰化和隐性EF-1基序。我们通过适当的突变来恢复残疾的EF-1环的Ca2 +结合能力，从而研究了神经钙传感器1（NCS-1）中这种相关性背后的基本原理。规范EF-1和N-肉豆蔻酰化的并发性大大降低了整体Ca2 +亲和力，构象柔韧性和下游效应分子（即PI4K beta）的功能激活。特别值得注意的是，在恢复了与EF-1的Ca2 +结合的肉豆蔻酰化蛋白质中，Ca2 +诱导的构象变化（这是将CaBP视为传感器的第一个前提）。此外，Ca2 +会增加PI4Kβ的酶促活性（由NCS-1调节），导致肉豆蔻酰化突变体（具有规范EF-1）的PI4K beta活性进一步下降，从而导致Ca2 +信号传导和在结构和功能层面上的特异性。这项研究建立了NCS-1中肉豆蔻酰化和EF-1隐秘之间强烈的联系。打破这种联系会导致尽管有Ca2 +结合，但Ca2 +特异性信号转导至下游效应分子的失败。因此，EF-1残疾是附加肉豆蔻酰化信号转导，同时在NCS-1中保留结构鲁棒性和Ca2 +敏感性/特异性的前提。

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