Localization of protein-binding sites within families of proteins
Localization of protein-binding sites within families of proteins
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DOI：
10.1110/ps.051571905
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Sali, A
中科院分区：
文献类型：
--
作者：
Korkin, D;Davis, FP;Sali, A
我们解决的问题，无论其结合伙伴的身份的同源蛋白质结构上的蛋白质结合位点的位置是保守的。首先，对于蛋白质结构分类（SCOP）中的每个结构域家族，从我们的结构定义的二元结构域相互作用（PIBASE）的综合数据库中提取蛋白质结合位点。第二，每个家族内的结合位点使用其成员的结构对齐来叠加。最后，每个家庭内的结合位点的本地化程度进行量化，通过比较它与本地化预期的机会。我们发现，72%的1847 SCOP结构域家族在PIBASE的结合位点的定位值大于预期的机会。此外，这些家庭中有554个（30%）具有统计学显著的定位（即，偏离偶然期望的平均值超过四个标准偏差）。相比之下，只有144个（8%）家庭的本地化程度明显较低。在一个家庭中的平均序列和结构保守的结合位点定位的显着相关性的情况下，表明本地化可以有助于描述蛋白质-蛋白质相互作用的功能多样性，补充措施的序列和结构保守。结合位点定位的考虑也可能导致蛋白质组装结构建模的空间限制。
We address the question of whether or not the positions of protein-binding sites on homologous protein structures are conserved irrespective of the identities of their binding partners. First, for each domain family in the Structural Classification of Proteins (SCOP), protein-binding sites are extracted from our comprehensive database of structurally defined binary domain interactions (PIBASE). Second, the binding sites within each family are superposed using a structural alignment of its members. Finally, the degree of localization of binding sites within each family is quantified by comparing it with localization expected by chance. We found that 72% of the 1847 SCOP domain families in PIBASE have binding sites with localization values greater than expected by chance. Moreover, 554 (30%) of these families have localizations that are statistically significant (i.e., more than four standard deviations away from the mean expected by chance). In contrast, only 144 (8%) families have significantly low localization. The absence of a significant correlation of the binding site localization with the average sequence and structural conservations in a family suggests that localization can be helpful for describing the functional diversity of protein-protein interactions, complementing measures of sequence and structural conservation. Consideration of the binding site localization may also result in spatial restraints for the modeling of protein assembly structures.