The many faces of protein-protein interactions: A compendium of interface geometry.
The many faces of protein-protein interactions: A compendium of interface geometry.
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DOI：
10.1371/journal.pcbi.0020124
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发表时间：
2006-09-29
影响因子：
4.3
通讯作者：
Schroeder M
中科院分区：
文献类型：
--
作者：
Kim WK;Henschel A;Winter C;Schroeder M
蛋白质-蛋白质界面的系统分类是理解分子识别原理和蛋白质复合物建模的宝贵资源。在这里，我们提出了一个分类的域接口根据其几何形状。我们的新算法使用了一种混合的方法，顺序和结构特征。准确性在416个接口的手工数据集上进行评估。我们的混合程序实现了83%的准确率和95%的召回率，这两个方面都将早期基于序列的方法提高了5%。我们分类几乎所有的域接口已知的结构，这导致近6,000种不同类型的接口。在40%的情况下，相互作用的结构域家族关联在多个方向，这表明所有可能的结合方向需要探索建模多结构域蛋白质和蛋白质复合物。一般来说，枢纽蛋白质被证明使用不同的表面区域（多个面）与不同的合作伙伴进行相互作用。我们的分类提供了一个方便的框架来查询真正的基因融合，它保存了融合和分离形式的结合方向。结果表明，在通过常规序列相似性搜索检测到的至少三分之一的基因融合案例中，结合方向不保守。我们表明，任何进化分析的接口，可以通过多个绑定方向和多个相互作用的合作伙伴倾斜。接口类型的分类分布表明，古老的接口共同的三大王国的生活是丰富的对称同源二聚体。分类结果可在http://www.scoppi.org上在线查看。生物系统的行为受蛋白质相互作用的控制。已经有相当多的努力致力于研究单个蛋白质及其进化。作为下一步，研究人员需要了解蛋白质复杂网络的特征，动力学和进化。虽然许多实验技术确定高通量的蛋白质-蛋白质相互作用，只有少数提供结构的见解实际接口。作者提供了这些结构界面的综合纲要和分类。为此，他们设计了一种快速准确的算法，并将其应用于所有已知的结构相互作用。因此，他们揭示了蛋白质界面的几何形状和进化。他们的分析表明，同源物之间40%的蛋白质相互作用在多个方向上相关。特别是，这对通过常规序列同源性检测的基因融合事件有影响：对于这些基因中的三分之一，融合和非融合蛋白质以替代结合方向相关联。该分类还表明，任何进化分析，如界面保守，可以通过多个绑定方向和相互作用的合作伙伴倾斜。枢纽蛋白，这是高度连接到许多其他蛋白质的相互作用网络，显示使用不同的表面，或面对不同的合作伙伴。有趣的是，一些蛋白质为同一伴侣开发了许多不同的面孔（例如，长链细胞因子和纤连蛋白），以及其他使用相同的面孔用于进化无关的伙伴（例如，普阿结构域家族）。最后，作者表明，古老的接口，这出现在所有三个王国的生活，占主导地位的对称同源二聚体，反映了从对称到不对称或异源的进化方向。
A systematic classification of protein–protein interfaces is a valuable resource for understanding the principles of molecular recognition and for modelling protein complexes. Here, we present a classification of domain interfaces according to their geometry. Our new algorithm uses a hybrid approach of both sequential and structural features. The accuracy is evaluated on a hand-curated dataset of 416 interfaces. Our hybrid procedure achieves 83% precision and 95% recall, which improves the earlier sequence-based method by 5% on both terms. We classify virtually all domain interfaces of known structure, which results in nearly 6,000 distinct types of interfaces. In 40% of the cases, the interacting domain families associate in multiple orientations, suggesting that all the possible binding orientations need to be explored for modelling multidomain proteins and protein complexes. In general, hub proteins are shown to use distinct surface regions (multiple faces) for interactions with different partners. Our classification provides a convenient framework to query genuine gene fusion, which conserves binding orientation in both fused and separate forms. The result suggests that the binding orientations are not conserved in at least one-third of the gene fusion cases detected by a conventional sequence similarity search. We show that any evolutionary analysis on interfaces can be skewed by multiple binding orientations and multiple interaction partners. The taxonomic distribution of interface types suggests that ancient interfaces common to the three major kingdoms of life are enriched by symmetric homodimers. The classification results are online at http://www.scoppi.org. The behaviour of biological systems is governed by protein interactions. Considerable effort has already been dedicated to characterise individual proteins and their evolution. As a next step, researchers need to understand the characteristics, dynamics, and evolution of complex networks of proteins. While many experimental techniques determine high-throughput protein–protein interactions, only few provide structural insights into the actual interfaces. The authors provide a comprehensive compendium and classification of these structural interfaces. To this end, they design a fast and accurate algorithm, which they apply to all known structural interactions. As a result, they shed light on the geometry and the evolution of protein interfaces. Their analysis reveals that 40% of protein interactions between homologues associate in multiple orientations. This has, in particular, implications for gene fusion events detected by conventional sequence homology: for one-third of these genes, the fused and nonfused proteins associate in alternative binding orientations. The classification also shows that any evolutionary analysis, such as interface conservation, can be skewed by multiple binding orientations and interaction partners. Hub proteins, which are highly connected to many other proteins in interaction networks, are shown to use distinct surfaces, or faces, for different partners. Interestingly, some proteins develop many different faces for the same partner (e.g., long-chain cytokines and fibronectin), and others use the same face for evolutionary unrelated partners (e.g., the PUA domain family). Finally, the authors show that ancient interfaces, which appear in all three kingdoms of life, are dominated by symmetric homodimers, reflecting the direction of evolution from symmetric to asymmetric or heteromeric.
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