Rules governing selective protein carbonylation.

Rules governing selective protein carbonylation.
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DOI:
10.1371/journal.pone.0007269
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发表时间:
2009-10-05
期刊:
影响因子:
3.7
通讯作者:
Dukan S
Dukan S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Maisonneuve E;Ducret A;Khoueiry P;Lignon S;Longhi S;Talla E;Dukan S

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羰基衍生物主要是通过直接金属催化氧化(MCO)攻击脯氨酸、精氨酸、赖氨酸和苏氨酸残基的氨基酸侧链而形成。由于未知的原因,只有一些蛋白质容易发生羰基化。我们使用质谱分析来鉴定:经过体外 MCO 的 BSA 和大肠杆菌中的 23 个羰基化蛋白质。羰基化位点的存在使得邻近的可羰基化位点更易于羰基化。大多数羰基化位点存在于羰基化热点内。这些观察结果使我们提出了识别更容易发生羰基化的位点的规则。我们使用这些规则设计了一个计算机模型(可在http://www.lcb.cnrs-mrs.fr/CSPD/获得),从而可以有效、准确地预测大肠杆菌蛋白质组中更容易发生羰基化的位点和蛋白质。我们观察到蛋白质进化为选择性地维持或失去预测的羰基化热点,具体取决于其生物学功能。由于我们的预测模型还可以有效检测枯草芽孢杆菌中的羰基化蛋白质,因此我们相信我们的模型可以扩展到所有生物体中的直接 MCO 攻击。
Carbonyl derivatives are mainly formed by direct metal-catalysed oxidation (MCO) attacks on the amino-acid side chains of proline, arginine, lysine and threonine residues. For reasons unknown, only some proteins are prone to carbonylation. We used mass spectrometry analysis to identify carbonylated sites in: BSA that had undergone in vitro MCO, and 23 carbonylated proteins in Escherichia coli. The presence of a carbonylated site rendered the neighbouring carbonylatable site more prone to carbonylation. Most carbonylated sites were present within hot spots of carbonylation. These observations led us to suggest rules for identifying sites more prone to carbonylation. We used these rules to design an in silico model (available at http://www.lcb.cnrs-mrs.fr/CSPD/), allowing an effective and accurate prediction of sites and of proteins more prone to carbonylation in the E. coli proteome. We observed that proteins evolve to either selectively maintain or lose predicted hot spots of carbonylation depending on their biological function. As our predictive model also allows efficient detection of carbonylated proteins in Bacillus subtilis, we believe that our model may be extended to direct MCO attacks in all organisms.
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