Evolutionarily conserved networks of residues mediate allosteric communication in proteins
Evolutionarily conserved networks of residues mediate allosteric communication in proteins
复制标题
DOI：
10.1038/nsb881
复制
发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Ranganathan, R
中科院分区：
文献类型：
--
作者：
Süel, GM;Lockless, SW;Ranganathan, R
细胞信号传导的一个基本目标是了解变构通讯，即源自蛋白质某一位点的信号可靠传播以影响远处功能位点的过程。这一过程背后的蛋白质结构的一般原理仍然未知。在这里，我们描述了一种基于序列的统计方法，用于定量绘制蛋白质中氨基酸相互作用的全局网络。将这种方法应用于三个结构和功能不同的蛋白质家族（G蛋白偶联受体、丝氨酸蛋白酶的胰凝乳蛋白酶类和血红蛋白），揭示了每个蛋白质家族中氨基酸相互作用的令人惊讶的简单结构：一小部分残基形成物理连接的网络，连接三级结构中遥远的功能位点。尽管数量很少，但组成网络的残基与每个家族可用的大量机械数据显示出良好的相关性。数据表明，进化上保守的氨基酸相互作用的稀疏网络代表了蛋白质中变构通讯的结构基序。
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Here, we describe a sequence-based statistical method for quantitatively mapping the global network of amino acid interactions in a protein. Application of this method for three structurally and functionally distinct protein families (G protein-coupled receptors, the chymotrypsin class of serine proteases and hemoglobins) reveals a surprisingly simple architecture for amino acid interactions in each protein family: a small subset of residues forms physically connected networks that link distant functional sites in the tertiary structure. Although small in number, residues comprising the network show excellent correlation with the large body of mechanistic data available for each family. The data suggest that evolutionarily conserved sparse networks of amino acid interactions represent structural motifs for allosteric communication in proteins.