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Protein kinases phosphorylate long disordered regions in intrinsically disordered proteins.
Protein Science ( IF 4.5 ) Pub Date : 2019-11-28 , DOI: 10.1002/pro.3789
Ryotaro Koike 1 , Mutsuki Amano 2 , Kozo Kaibuchi 2 , Motonori Ota 1
Affiliation  

Phosphorylation is a major post-translational modification that plays a central role in signaling pathways. Protein kinases phosphorylate substrates (phosphoproteins) by adding phosphate at Ser/Thr or Tyr residues (phosphosites). A large amount of data identifying and describing phosphosites in phosphoproteins has been reported but the specificity of phosphorylation is not fully resolved. In this report, data of kinase-substrate pairs identified by the Kinase-Interacting Substrate Screening (KISS) method were used to analyze phosphosites in intrinsically disordered regions (IDRs) of intrinsically disordered proteins. We compared phosphorylated and nonphosphorylated IDRs and found that the phosphorylated IDRs were significantly longer than nonphosphorylated IDRs. The phosphorylated IDR is often the longest IDR (71%) in a phosphoprotein when only a single phosphosite exists in the IDR, and when the phosphoprotein has multiple phosphosites in an IDR(s), the phosphosites are primarily localized in a single IDR (78%) and this IDR is usually the longest one (81%). We constructed a stochastic model of phosphorylation to estimate the effect of IDR length. The model that accounted for IDR length produced more realistic results when compared with a model that excluded the IDR length. We propose that the IDR length is a significant determinant for locating kinase phosphorylation sites in phosphoproteins.

中文翻译:

蛋白激酶磷酸化内在无序蛋白中的长无序区域。

磷酸化是主要的翻译后修饰,在信号传导途径中起着核心作用。蛋白激酶通过在Ser / Thr或Tyr残基(亚磷酸酯)处添加磷酸来使底物(磷酸蛋白)磷酸化。已经报道了鉴定和描述磷蛋白中磷酸位的大量数据,但是磷酸化的特异性尚未完全解决。在本报告中,通过激酶相互作用底物筛选(KISS)方法鉴定的激酶-底物对数据用于分析内在无序蛋白的内在无序区域(IDR)中的磷酸位。我们比较了磷酸化和非磷酸化的IDR,发现磷酸化的IDR明显长于非磷酸化的IDR。当IDR中仅存在一个磷酸位点时,磷酸化IDR通常是磷蛋白中最长的IDR(71%),并且当一个IDR中的磷酸化蛋白具有多个磷酸位点时,磷酸化位点主要位于单个IDR中(78 %),而该IDR通常是最长的IDR(81%)。我们构建了磷酸化的随机模型,以估计IDR长度的影响。与排除IDR长度的模型相比,考虑了IDR长度的模型产生了更为真实的结果。我们建议IDR长度是在磷酸蛋白中定位激酶磷酸化位点的重要决定因素。我们构建了磷酸化的随机模型来估计IDR长度的影响。与排除IDR长度的模型相比,考虑了IDR长度的模型产生了更为真实的结果。我们建议IDR长度是在磷酸蛋白中定位激酶磷酸化位点的重要决定因素。我们构建了磷酸化的随机模型来估计IDR长度的影响。与排除IDR长度的模型相比,考虑了IDR长度的模型产生了更为真实的结果。我们建议IDR长度是在磷酸蛋白中定位激酶磷酸化位点的重要决定因素。
更新日期:2020-01-13
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