Alignment of major-groove hydrogen bond arrays uncovers shared information between different DNA sequences that bind the same protein.
Alignment of major-groove hydrogen bond arrays uncovers shared information between different DNA sequences that bind the same protein.
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DOI：
10.1093/nargab/lqac101
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发表时间：
2022-12
影响因子：
4.6
通讯作者：
Solomon, Lee A.
中科院分区：
文献类型：
--
作者：
Sedhom, Jacklin;Kinser, Jason;Solomon, Lee A.
由于蛋白质- dna结合在许多生物过程中的重要性，它引起了人们的极大兴趣。先前的研究已经提出了许多因素负责识别和特异性，但了解结合多个dna位点的蛋白质的最小信息需求仍然是生物信息学的一个未充分研究的领域。在这里，我们主要关注目标DNA在主要凹槽中显示的参与蛋白质结合的氢键。我们表明，集中于碱基对同一性的分析可能会忽略关键的氢键。我们开发了一种算法，可以将核苷酸序列转化为一系列氢键供体，受体和甲基。然后对这些非共价相互作用阵列进行比对，以确定在多个DNA序列中维持的信息。对于三种不同的dna结合蛋白，乳糖抑制蛋白、控制蛋白和λ-CI抑制蛋白，我们发现了所有结合序列中常见的最小氢键模式。值得注意的是，在这三种蛋白质中，尽管相应的结合位点发生了核碱基突变，但关键的相互作用氢键仍能维持。我们相信这项工作将有助于开发新的DNA结合蛋白，并为进化关系提供新的线索。
Protein–DNA binding is of a great interest due to its importance in many biological processes. Previous studies have presented many factors responsible for the recognition and specificity, but understanding the minimal informational requirements for proteins that bind to multiple DNA-sites is still an understudied area of bioinformatics. Here we focus on the hydrogen bonds displayed by the target DNA in the major groove that take part in protein-binding. We show that analyses focused on the base pair identity may overlook key hydrogen bonds. We have developed an algorithm that converts a nucleotide sequence into an array of hydrogen bond donors and acceptors and methyl groups. It then aligns these non-covalent interaction arrays to identify what information is being maintained among multiple DNA sequences. For three different DNA-binding proteins, Lactose repressor, controller protein and λ-CI repressor, we uncovered the minimal pattern of hydrogen bonds that are common amongst all the binding sequences. Notably in the three proteins, key interacting hydrogen bonds are maintained despite nucleobase mutations in the corresponding binding sites. We believe this work will be useful for developing new DNA binding proteins and shed new light on evolutionary relationships.
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影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE
影响因子：
4
作者：
Kumar, Sachin;Bhardwaj, Vijay K.;Purohit, Rituraj
通讯作者：
Purohit, Rituraj
影响因子：
1.1
作者：
Fattah, KR;Mizutani, S;Sugino, Y
通讯作者：
Sugino, Y
影响因子：
14.9
作者：
Ball, N. J.;McGeehan, J. E.;Kneale, G. G.
通讯作者：
Kneale, G. G.