Protein-protein interaction hotspots carved into sequences.
Protein-protein interaction hotspots carved into sequences.
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DOI：
10.1371/journal.pcbi.0030119
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发表时间：
2007-07
影响因子：
4.3
通讯作者：
Rost B
中科院分区：
文献类型：
--
作者：
Ofran Y;Rost B
蛋白质之间的相互作用是几乎所有生物过程的关键，它是由分子机制介导的，目前尚不完全清楚。这些机制的研究通常集中在蛋白质-蛋白质界面的所有残基上。然而，所有界面残基中只有一小部分是识别或结合所必需的。通常被称为“热点”，这些基本残基被定义为在突变时阻碍蛋白质相互作用的残基。虽然没有计算机工具识别未结合链中的热点，但设计了许多预测方法来识别蛋白质中可能成为蛋白质-蛋白质界面一部分的所有残基。这些方法通常只能成功地识别所有界面残留物的一小部分。在这里，我们分析了两个子集对应的假设（即，计算机方法可能预测很少的残数，因为它们优先预测热点）。我们证明确实如此，因此我们可以直接从单个蛋白质的序列预测哪些残基是相互作用热点（不知道相互作用伙伴）。我们的结果表明，大多数蛋白质复合物都是通过类似的基本原理稳定的。准确有效地从序列中识别热点的能力，使整个生物体中蛋白质-蛋白质相互作用热点的注释和分析成为可能，从而有利于功能预测和药物开发。用于预测的服务器可在http://www.rostlab.org/services/isis上获得。蛋白质之间的相互作用是所有生物过程的基础。因此，为了充分理解或控制生物过程，我们需要解开蛋白质相互作用的原理。对这些原理的探索主要集中在两个相互作用的蛋白质之间的整个界面上。然而，已经证明只有少数的界面残基是识别和结合其他蛋白质所必需的。这些残基的识别，通常被称为结合“热点”，是了解蛋白质功能和研究它们之间相互作用的第一步。实验上，热点可以通过突变单个残基来识别，这是一个昂贵而费力的过程，不适用于大规模。在这里，我们展示了在不需要了解其相互作用伙伴的情况下，基于单个蛋白质的氨基酸序列大规模计算识别蛋白质相互作用热点是可能的。我们的结果表明，大多数蛋白质复合物是由类似的基本原理稳定的。准确有效地从序列中识别热点的能力，使整个生物体中蛋白质-蛋白质相互作用热点的注释和分析成为可能，从而有利于功能预测和药物开发。
Protein–protein interactions, a key to almost any biological process, are mediated by molecular mechanisms that are not entirely clear. The study of these mechanisms often focuses on all residues at protein–protein interfaces. However, only a small subset of all interface residues is actually essential for recognition or binding. Commonly referred to as “hotspots,” these essential residues are defined as residues that impede protein–protein interactions if mutated. While no in silico tool identifies hotspots in unbound chains, numerous prediction methods were designed to identify all the residues in a protein that are likely to be a part of protein–protein interfaces. These methods typically identify successfully only a small fraction of all interface residues. Here, we analyzed the hypothesis that the two subsets correspond (i.e., that in silico methods may predict few residues because they preferentially predict hotspots). We demonstrate that this is indeed the case and that we can therefore predict directly from the sequence of a single protein which residues are interaction hotspots (without knowledge of the interaction partner). Our results suggested that most protein complexes are stabilized by similar basic principles. The ability to accurately and efficiently identify hotspots from sequence enables the annotation and analysis of protein–protein interaction hotspots in entire organisms and thus may benefit function prediction and drug development. The server for prediction is available at http://www.rostlab.org/services/isis. Interactions between proteins underlie all biological processes. Hence, to fully understand or to control biological processes we need to unravel the principles of protein interactions. The quest for these principles has focused predominantly on the entire interfaces between two interacting proteins. However, it has been shown that only few of the interface residues are essential for the recognition and binding to other proteins. The identification of these residues, commonly referred to as binding “hotspots,” is a first step toward understanding the function of proteins and studying their interactions. Experimentally, hotspots could be identified by mutating single residues—an expensive and laborious procedure that is not applicable on a large scale. Here, we show that it is possible to identify protein interaction hotspots computationally on a large scale based on the amino acid sequence of a single protein, without requiring the knowledge of its interaction partner. Our results suggest that most protein complexes are stabilized by similar basic principles. The ability to accurately and efficiently identify hotspots from sequence enables the annotation and analysis of protein–protein interaction hotspots in an entire organism and thus may benefit function prediction and drug development.
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影响因子：
64.8
作者：
Gavin, AC;Bösche, M;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
2.4
作者：
Koike, A;Takagi, T
通讯作者：
Takagi, T
DOI：
10.1073/pnas.092147999
发表时间：
2002-04-30
影响因子：
11.1
作者：
Aloy, P;Russell, RB
通讯作者：
Russell, RB
DOI：
10.1093/protein/13.12.839
发表时间：
2000-12-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Innis, CA;Shi, JY;Blundell, TL
通讯作者：
Blundell, TL
影响因子：
5.6
作者：
Lichtarge, O;Bourne, HR;Cohen, FE
通讯作者：
Cohen, FE