酵母蛋白-蛋白相互作用网络中界面重叠与功能分化的关系

IF 4.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2025-09-17 DOI:10.1016/j.str.2025.08.019

Yilun Han, Mohamed Ghadie, Yu Xia

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引用次数: 0

摘要

蛋白质-蛋白质相互作用（PPIs）和遗传相互作用是细胞功能的核心。我们研究了它们在酵母PPI网络结构上的关系，特别是PPI结构分化和功能分化之间的关系。对于结合相同靶蛋白的蛋白质对（“相互作用物对”），我们使用界面重叠（相互作用物对之间共享的靶蛋白中的界面残基数量）来测量PPI结构差异，并使用遗传相互作用谱相似性来测量功能差异。我们发现界面重叠与遗传相互作用谱相似性之间存在显著且强大的负相关，其中在目标蛋白上具有较大共享界面的相互作用因子对倾向于执行不同的表型水平功能。这种关系是最强的，当功能相似性是由基因相互作用谱相似性测量，而不是由基因本体为基础的功能相似性。我们的研究结果表明，竞争结合在表型水平上驱动蛋白质的功能分化。

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The relationship between interfacial overlap and functional divergence in the yeast protein-protein interaction network

Protein-protein interactions (PPIs) and genetic interactions are central to cellular function. We investigate their relationship in the structurally resolved yeast PPI network, specifically the relationship between PPI structural divergence and functional divergence. For pairs of proteins (“interactor pairs”) binding to the same target protein, we measure PPI structural divergence using interfacial overlap (the number of interfacial residues in the target protein shared between the interactor pair), and functional divergence using genetic interaction profile similarity. We find a significant and robust negative correlation between interfacial overlap and genetic interaction profile similarity, where interactor pairs with large shared interface on the target protein tend to perform divergent phenotypic-level functions. This relationship is the strongest when functional similarity is measured by genetic interaction profile similarity, rather than by gene ontology-based functional similarity. Our findings suggest that competitive binding drives functional divergence of proteins at the phenotypic level.

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.