构建蛋白质重复序列的选择性剪接和进化感知序列结构图

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Antoine Szatkownik , Diego Javier Zea , Hugues Richard , Elodie Laine
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引用次数: 0

摘要

蛋白质中重复序列的选择性剪接提供了重新布线和微调蛋白质相互作用网络的机制。在这项工作中,我们开发了一种强大而通用的方法ASPRING,用于从基因注释中识别选择性剪接的蛋白质重复序列。ASPRING利用进化意义上的选择性剪接感知层次图来提供蛋白质重复序列和3D结构之间的映射。我们通过明确考虑几个基因/物种的转录多样性来重新思考重复序列的定义。使用严格的基于序列的相似性标准,我们通过筛选十几个物种中几乎所有的人类蛋白质编码基因及其直系同源物,检测到了5000多个进化保守重复序列。通过对它们的序列和结构的联合分析,我们提取了决定序列特征的特异性,并评估了它们在实验解析和模拟蛋白质相互作用中的意义。我们的发现证明了蛋白质重复序列在调节蛋白质相互作用中的广泛替代用途,并为靶向重复序列介导的相互作用开辟了途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Building alternative splicing and evolution-aware sequence-structure maps for protein repeats

Building alternative splicing and evolution-aware sequence-structure maps for protein repeats

Alternative splicing of repeats in proteins provides a mechanism for rewiring and fine-tuning protein interaction networks. In this work, we developed a robust and versatile method, ASPRING, to identify alternatively spliced protein repeats from gene annotations. ASPRING leverages evolutionary meaningful alternative splicing-aware hierarchical graphs to provide maps between protein repeats sequences and 3D structures. We re-think the definition of repeats by explicitly accounting for transcript diversity across several genes/species. Using a stringent sequence-based similarity criterion, we detected over 5,000 evolutionary conserved repeats by screening virtually all human protein-coding genes and their orthologs across a dozen species. Through a joint analysis of their sequences and structures, we extracted specificity-determining sequence signatures and assessed their implication in experimentally resolved and modelled protein interactions. Our findings demonstrate the widespread alternative usage of protein repeats in modulating protein interactions and open avenues for targeting repeat-mediated interactions.

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来源期刊
Journal of structural biology
Journal of structural biology 生物-生化与分子生物学
CiteScore
6.30
自引率
3.30%
发文量
88
审稿时长
65 days
期刊介绍: Journal of Structural Biology (JSB) has an open access mirror journal, the Journal of Structural Biology: X (JSBX), sharing the same aims and scope, editorial team, submission system and rigorous peer review. Since both journals share the same editorial system, you may submit your manuscript via either journal homepage. You will be prompted during submission (and revision) to choose in which to publish your article. The editors and reviewers are not aware of the choice you made until the article has been published online. JSB and JSBX publish papers dealing with the structural analysis of living material at every level of organization by all methods that lead to an understanding of biological function in terms of molecular and supermolecular structure. Techniques covered include: • Light microscopy including confocal microscopy • All types of electron microscopy • X-ray diffraction • Nuclear magnetic resonance • Scanning force microscopy, scanning probe microscopy, and tunneling microscopy • Digital image processing • Computational insights into structure
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