Park J, Lappe M, Teichmann S A
European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SD, UK.
J Mol Biol. 2001 Mar 30;307(3):929-38. doi: 10.1006/jmbi.2001.4526.
In the postgenomic era, one of the most interesting and important challenges is to understand protein interactions on a large scale. The physical interactions between protein domains are fundamental to the workings of a cell: in multi-domain polypeptide chains, in multi-subunit proteins and in transient complexes between proteins that also exist independently. To study the large-scale patterns and evolution of interactions between protein domains, we view interactions between protein domains in terms of the interactions between structural families of evolutionarily related domains. This allows us to classify 8151 interactions between individual domains in the Protein Data Bank and the yeast Saccharomyces cerevisiae in terms of 664 types of interactions, between protein families. At least 51 interactions do not occur in the Protein Data Bank and can only be derived from the yeast data. The map of interactions between protein families has the form of a scale-free network, meaning that most protein families only interact with one or two other families, while a few families are extremely versatile in their interactions and are connected to many families. We observe that almost half of all known families engage in interactions with domains from their own family. We also see that the repertoires of interactions of domains within and between polypeptide chains overlap mostly for two specific types of protein families: enzymes and same-family interactions. This suggests that different types of protein interaction repertoires exist for structural, functional and regulatory reasons.
在后基因组时代，最有趣且重要的挑战之一是大规模理解蛋白质相互作用。蛋白质结构域之间的物理相互作用是细胞运作的基础：存在于多结构域多肽链、多亚基蛋白质以及同样独立存在的蛋白质之间的瞬时复合物中。为了研究蛋白质结构域之间相互作用的大规模模式和进化，我们从进化相关结构域的结构家族之间的相互作用角度来审视蛋白质结构域之间的相互作用。这使我们能够根据蛋白质家族之间664种相互作用类型，对蛋白质数据库（Protein Data Bank）和酿酒酵母（Saccharomyces cerevisiae）中单个结构域之间的8151种相互作用进行分类。蛋白质数据库中至少有51种相互作用未出现，只能从酵母数据中推导得出。蛋白质家族之间的相互作用图谱具有无标度网络的形式，这意味着大多数蛋白质家族仅与一两个其他家族相互作用，而少数家族在相互作用方面极具通用性，与许多家族相连。我们观察到，几乎所有已知家族中有近一半与来自其自身家族的结构域发生相互作用。我们还发现，多肽链内和链间结构域的相互作用库在两种特定类型的蛋白质家族中大多重叠：酶和同家族相互作用。这表明，出于结构、功能和调节方面的原因，存在不同类型的蛋白质相互作用库。
