Screening a Protein Array with Synthetic Biotinylated Inorganic Polyphosphate To Define the Human PolyP-ome
Screening a Protein Array with Synthetic Biotinylated Inorganic Polyphosphate To Define the Human PolyP-ome
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DOI：
10.1021/acschembio.8b00357
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Saiardi, Adolfo
中科院分区：
文献类型：
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作者：
Azevedo, Cristina;Singh, Jyoti;Saiardi, Adolfo
表型是通过对蛋白质功能的严格调节来建立的。这种调节可以通过蛋白质结合变构介导，也可以通过翻译后修饰（PTM）共价介导。越来越多的PTM整合到调控网络中，使蛋白质组的复杂性得以实现并定义。蛋白质PTM可以酶促和非酶促发生。多磷酸化是最近发现的属于后一类别的PTM，是称为无机多磷酸盐（polyP）的线性正磷酸盐聚合物与赖氨酸残基的共价连接。PolyP在自然界中普遍存在，也已知其变构控制蛋白质功能。迄今为止，试剂的缺乏阻碍了与聚P共价和/或变构相关的蛋白质的系统分析。在这里，我们报告了生物素修饰的单分散短链聚P（生物-聚P8-生物）的化学合成及其随后用于筛选人类蛋白质组阵列以识别与聚P相关的蛋白质，从而开始定义人类聚P组。
Phenotypes are established by tight regulation on protein functions. This regulation can be mediated allosterically, through protein binding, and covalently, through post-translational modification (PTM). The integration of an ever-increasing number of PTMs into regulatory networks enables and defines the proteome complexity. Protein PTMs can occur enzymatically and nonenzymatically. Polyphosphorylation, which is a recently discovered PTM that belongs to the latter category, is the covalent attachment of the linear ortho-phosphate polymer called inorganic polyphosphate (polyP) to lysine residues. PolyP, which is ubiquitously present in nature, is also known to allosterically control protein function. To date, lack of reagents has prevented the systematic analysis of proteins covalently and/or allosterically associated with polyP. Here, we report on the chemical synthesis of biotin-modified monodisperse short-chain polyP (bio-polyP8-bio) and its subsequent use to screen a human proteome array to identify proteins that associate with polyP, thereby starting to define the human polyP-ome.