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Conformational heterogeneity in tails of DNA-binding proteins is augmented by proline containing repeats
Molecular BioSystems Pub Date : 2017-10-26 00:00:00 , DOI: 10.1039/c7mb00412e
Harshavardhan Khare 1, 2, 3, 4 , Debayan Dey 1, 2, 3, 4 , Chilakapati Madhu 4, 5, 6, 7, 8 , Dillip Senapati 1, 2, 3, 4, 9 , Srinivasarao Raghothama 2, 3, 4, 9 , Thimmaiah Govindaraju 4, 5, 6, 7, 8 , Suryanarayanarao Ramakumar 1, 2, 3, 4
Affiliation  

A cationic terminal extension or tail is a common feature of many DNA-binding proteins. We show that a particular type of tail rich in proline, alanine and lysine belongs to the class of ‘flexible disorder’ and consists of characteristic pentapeptide repeats. Our designed peptides, (AAKKA)1–4 and (PAKKA)1–4, represent the tails of several bacterial DNA-binding proteins. Enhanced conformational sampling of these representative peptides using accelerated molecular dynamic simulations supported by circular dichroism spectroscopy and nuclear magnetic resonance studies demonstrates the role of frequent and interspersed prolines in augmenting conformational heterogeneity of the peptide backbone. Analysis of circular variance of backbone dihedral angles indicates alternating regions of relative rigidity and flexibility along the peptide sequence due to prolines. Preferred placement of lysines in the regions of higher backbone flexibility might improve DNA-binding by conformational selection. Our results could be relevant for rational de novo design of disordered peptides.

中文翻译:

含脯氨酸的重复序列增加了DNA结合蛋白尾部的构象异质性

阳离子末端延伸或尾巴是许多DNA结合蛋白的共同特征。我们表明,富含脯氨酸,丙氨酸和赖氨酸的一种特殊类型的尾巴属于“柔性疾病”类别,由特征性五肽重复序列组成。我们设计的肽(AAKKA)1-4和(PAKKA)1-4代表几种细菌DNA结合蛋白的尾巴。这些代表性肽的增强构象采样使用圆二色谱和核磁共振研究支持的加速分子动力学模拟,证明了频繁和散布的脯氨酸在增强肽主链构象异质性中的作用。对主链二面角的圆形变化的分析表明,由于脯氨酸,沿肽序列的相对刚性和柔性的交替区域。赖氨酸在较高的骨架柔性区域中的优选放置可通过构象选择改善DNA结合。我们的结果可能与无序肽的合理从头设计有关。
更新日期:2017-11-21
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