Net Charge and Nonpolar Content Guide the Identification of Folded and Prion Proteins
Net Charge and Nonpolar Content Guide the Identification of Folded and Prion Proteins
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净电荷和非极性含量指导折叠蛋白和朊病毒蛋白的识别
DOI：
10.1021/acs.biochem.9b01114
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Cavagnero, Silvia
中科院分区：
文献类型：
--
作者：
Yaeger-Weiss, Susanna K.;Jennaro, Theodore S.;Mecha, Miranda;Becker, Jenna H.;Yang, Hanming;Winkler, Gordon L.;Cavagnero, Silvia
疏水性程度和每个残基的净电荷是能够仅基于氨基酸序列区分折叠蛋白质和固有无序蛋白质（IDP）的物理性质。在这里，我们通过采用Rose等人的非极性含量尺度并考虑氨基酸侧链的酸碱性，改进了基于上述参数的蛋白质和IDP的现有分类。由此产生的算法，在这里表示为净电荷非极性或NECNOP，使得能够在生理相关条件下以>95%的准确度简单预测蛋白质的折叠和无序状态，仅基于氨基酸序列。NECNOP方法对于具有>140个残基的蛋白质显示出大大增强的性能，这表明小蛋白质更可能具有不规则电荷和疏水性特征。对整个大肠杆菌蛋白质组的NECNOP分析确定了可溶性、完整膜和非完整膜蛋白特有的净电荷和非极性区域。令人惊讶的是，蛋白质的净电荷和疏水性被发现收敛到特定的值，随着链长的增加，在整个E。大肠杆菌蛋白质组此外，NECNOP图能够直接识别对应于朊病毒蛋白的蛋白质序列，并有望成为设计大蛋白质的强大预测工具。总之，NECNOP图是一种直接的方法，它提高了我们对蛋白质的氨基酸序列和三维结构之间关系的理解，作为分子量的函数。
The degree of hydrophobicity and net charge per residue are physical properties that enable the discrimination of folded from intrinsically disordered proteins (IDPs) solely on the basis of amino acid sequence. Here, we improve upon the existing classification of proteins and IDPs based on the parameters mentioned above by adopting the scale of nonpolar content of Rose et al. and by taking amino acid side-chain acidity and basicity into account. The resulting algorithm, denoted here as net charge nonpolar or NECNOP, enables the facile prediction of the folded and disordered status of proteins under physiologically relevant conditions with >95% accuracy, based on amino-acid sequence alone. The NECNOP approach displays a much-enhanced performance for proteins with >140 residues, suggesting that small proteins are more likely to have irregular charge and hydrophobicity features. NECNOP analysis of the entireEscherichia coliproteome identifies specific net charge and nonpolar regions peculiar to soluble, integral membrane, and non-integral membrane proteins. Surprisingly, protein net charge and hydrophobicity are found to converge to specific values as chain length increases, across theE. coliproteome. In addition, NECNOP plots enable the straightforward identification of protein sequences corresponding to prion proteins and promise to serve as a powerful predictive tool for the design of large proteins. In summary, NECNOP plots are a straightforward approach that improves our understanding of the relation between the amino acid sequence and three-dimensional structure of proteins as a function of molecular mass.