Dehydron:: A structurally encoded signal for protein interaction
Dehydron:: A structurally encoded signal for protein interaction
复制标题
DOI：
10.1016/s0006-3495(03)74619-0
复制
发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Scott, R
中科院分区：
文献类型：
--
作者：
Fernández, A;Scott, R
我们引入一个量子。一种称为“非对称”的结构基序，被证明是蛋白质-蛋白质相互作用的中心。脱水子是一种有缺陷的骨架氢键，表明预先形成的单体结构，其库仑能对结合诱导的水排斥高度敏感。这种预先形成的氢键是有效的粘合剂，因为从它们附近除去水有助于它们的稳定性。在结构水平，一个显着的相关性之间建立了连接子和网站的蛋白质复合物，与HIV-1衣壳蛋白P24与抗体轻链FAB 25.3复合提供了最显着的相关性。此外，来自不同物种的同源相似折叠蛋白质中的脱水子数量被证明是蛋白质组复杂性的标志。然后将该技术应用于更高水平的组织：衣壳的形成及其在小核糖核酸病毒中的组织与病毒单位边缘上的病毒颗粒的分布密切相关。此外，抗体接触和晶体接触可以被分配给衣壳组装后仍然普遍存在的衣壳。强调了在蛋白质组学、生物信息学和抑制剂药物设计中作为编码信号的pepson的意义。
We introduce a quanti. able structural motif, called dehydron, that is shown to be central to protein-protein interactions. A dehydron is a defectively packed backbone hydrogen bond suggesting preformed monomeric structure whose Coulomb energy is highly sensitive to binding-induced water exclusion. Such preformed hydrogen bonds are effectively adhesive, since water removal from their vicinity contributes to their stability. At the structural level, a significant correlation is established between dehydrons and sites for protein complexation, with the HIV-1 capsid protein P24 complexed with antibody light-chain FAB25.3 providing the most dramatic correlation. Furthermore, the number of dehydrons in homologous similar-fold proteins from different species is shown to be a signature of proteomic complexity. The techniques are then applied to higher levels of organization: The formation of the capsid and its organization in picornaviruses correlates strongly with the distribution of dehydrons on the rim of the virus unit. Furthermore, antibody contacts and crystal contacts may be assigned to dehydrons still prevalent after the capsid has been assembled. The implications of the dehydron as an encoded signal in proteomics, bioinformatics, and inhibitor drug design are emphasized.