Fernández Ariel, Scott Ridgway
Institute for Biophysical Dynamics, The University of Chicago, Illinois 60637, USA.
Biophys J. 2003 Sep;85(3):1914-28. doi: 10.1016/S0006-3495(03)74619-0.
We introduce a quantifiable 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.
我们引入了一种可量化的结构基序，称为脱水子，它被证明是蛋白质-蛋白质相互作用的核心。脱水子是一种堆积有缺陷的主链氢键，表明其单体结构已预先形成，其库仑能对结合诱导的水排除高度敏感。这种预先形成的氢键具有有效的粘附性，因为从其附近去除水有助于其稳定性。在结构层面上，脱水子与蛋白质复合位点之间建立了显著的相关性，其中HIV-1衣壳蛋白P24与抗体轻链FAB25.3复合的情况提供了最显著的相关性。此外，来自不同物种的同源相似折叠蛋白中的脱水子数量被证明是蛋白质组复杂性的一个标志。然后将这些技术应用于更高层次的组织：微小核糖核酸病毒中衣壳的形成及其组织与病毒单元边缘脱水子的分布密切相关。此外，衣壳组装后仍普遍存在的脱水子可被确定为抗体接触点和晶体接触点。文中强调了脱水子作为蛋白质组学、生物信息学和抑制剂药物设计中一种编码信号的意义。
