Similar binding sites and different partners: Implications to shared proteins in cellular pathways

被引:117
作者
Keskin, Ozlem [1 ]
Nussinov, Ruth
机构
[1] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Sariyer, Turkey
[2] Coll Engn, Rumelifeneri Yolu, TR-34450 Sariyer, Turkey
[3] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA
[4] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel
关键词
D O I
10.1016/j.str.2007.01.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:341 / 354
页数:14
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