Phosphorylated aspartate in the structure of a response regulator protein
Phosphorylated aspartate in the structure of a response regulator protein
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DOI：
10.1006/jmbi.1999.3261
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发表时间：
1999-11-19
影响因子：
5.6
通讯作者：
Wilkinson, AJ
中科院分区：
文献类型：
--
作者：
Lewis, RJ;Brannigan, JA;Wilkinson, AJ
天冬氨酸残基的磷酸化是双组分信号转导系统的标志，该系统协调微生物对其周围环境变化的适应性反应。双组分系统由解释环境信号的传感器激酶和激活适当生理反应的反应调节器组成。虽然反应调节因子的结构是已知的，但由于酸性磷酸盐连接的内在不稳定性，对其活化磷酸化形式知之甚少。在这里，我们报道了嗜热脂肪芽孢杆菌孢子形成的主要调节因子Spo0A的受体/磷受体结构域的磷酸化结构。磷酰基共价与不变的天冬氨酸55结合，并与附近的二价金属阳离子配位，两种物质通过与溶剂水分子、蛋白质主链和响应调节因子家族中高度保守的氨基酸残基侧链相互作用来实现其静电势。这是首次在任何蛋白质中直接看到与天冬氨酸残基共价连接的磷酸化基团，这对反应调节因子家族中的信号传导具有重要意义。(C) 1999学术出版社。
Phosphorylation of aspartic acid residues is the hallmark of two-component signal transduction systems that orchestrate the adaptive responses of micro-organisms to changes in their surroundings. Two-component systems consist of a sensor kinase that interprets environmental signals and a response regulator that activates the appropriate physiological response. Although structures of response regulators are known, little is understood about their activated phosphorylated forms, due to the intrinsic instability of the acid phosphate linkage. Here, we report the phosphorylated structure of the receiver/phosphoacceptor domain of Spo0A, the master regulator of sporulation, from Bacillus stearothermophilus. The phosphoryl group is covalently bonded to the invariant aspartate 55, and co-ordinated to a nearby divalent metal cation, with both species fulfilling their electrostatic potential through interactions with solvent water molecules, the protein main chain, and with side-chains of amino acid residues strongly conserved across the response regulator family. This is the first direct visualisation of a phosphoryl group covalently linked to an aspartic acid residue in any protein, with implications for signalling within the response regulator family. (C) 1999 Academic Press.