Keskin Ozlem, Nussinov Ruth
Koc University, Center for Computational Biology and Bioinformatics and College of Engineering, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.
Structure. 2007 Mar;15(3):341-54. doi: 10.1016/j.str.2007.01.007.
We studied a data set of structurally similar interfaces that bind to proteins with different binding-site structures and different functions. Our multipartner protein interface clusters enable us to address questions like: What makes a given site bind different proteins? How similar/different are the interactions? And, what drives the apparently less-specific association? We find that proteins with common binding-site motifs preferentially use conserved interactions at similar interface locations, despite the different partners. Helices are major vehicles for binding different partners, allowing alternate ways to achieve favorable association. The binding sites are characterized by imperfect packing, planar architectures, bridging water molecules, and, on average, smaller size. Interestingly, analysis of the connectivity of these proteins illustrates that they have more interactions with other proteins. These findings are important in predicting "date hubs," if we assume that "date hubs" are shared proteins with binding sites capable of transient binding to multipartners, linking higher-order networks.
我们研究了一组结构相似的界面数据集，这些界面与具有不同结合位点结构和不同功能的蛋白质结合。我们的多伙伴蛋白质界面簇使我们能够解决诸如以下问题：是什么使得给定的位点能结合不同的蛋白质？相互作用有多相似/不同？以及，是什么驱动了这种明显特异性较低的结合？我们发现，具有共同结合位点基序的蛋白质，尽管结合的伙伴不同，但它们优先在相似的界面位置使用保守的相互作用。螺旋是结合不同伙伴的主要载体，允许通过多种方式实现有利的结合。这些结合位点的特征在于堆积不完美、平面结构、桥连水分子，并且平均尺寸较小。有趣的是，对这些蛋白质连接性的分析表明，它们与其他蛋白质有更多的相互作用。如果我们假设“约会枢纽”是具有能够与多个伙伴瞬时结合的位点的共享蛋白质，连接高阶网络，那么这些发现对于预测“约会枢纽”很重要。
