The propagation of binding interactions to remote sites in proteins: Analysis of the binding of the monoclonal antibody D1.3 to lysozyme
The propagation of binding interactions to remote sites in proteins: Analysis of the binding of the monoclonal antibody D1.3 to lysozyme
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DOI：
10.1073/pnas.96.18.10118
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发表时间：
1999-08-31
影响因子：
11.1
通讯作者：
Freire, E
中科院分区：
文献类型：
--
作者：
Freire, E
配体与蛋白质的相互作用发生在局部位点（结合位点）并且仅涉及少数残基；然而，这种相互作用的影响通常会传播到远程位置。由结合引发的一系列事件为基本生物现象（如变构、信号转导和结构稳定性修饰）提供了基础。在本文中，提出了一种基于结构的统计热力学方法，并用于预测单克隆抗体 D1.3 与鸡蛋清溶菌酶结合所引发的稳定效应的传播，此前，Williams 等人。 [Williams, D. C.、Benjamin, D. C.、Poljak, R. J, & Rule, GI S. (1996) J. Mol. Biol, 257, 866-876]表明该抗体的结合会影响鸡蛋清溶菌酶的稳定性，并且结合效应会传播到距离结合表位较远位置的选定数量的残基。在本文中，我表明可以从结构中预测这种现象。这里提出的形式允许识别源自结合位点的合作相互作用所遵循的结构路径。结果表明，结合效应传播到远端区域的一个重要条件是在未复合的结合位点中存在相当一部分具有低结构稳定性的残基。对蛋白质结构的调查表明，许多结合位点具有双重特征，并且由高结构稳定性区域和低结构稳定性区域定义。低稳定性区域可能参与将结合信息传递到蛋白质中的其他区域。
The interaction of a ligand with a protein occurs at a local site (the binding site) and involves only a few residues; however, the effects of that interaction are often propagated to remote locations, The chain of events initiated by binding provides the basis for fundamental biological phenomena such as allosterism, signal transduction, and structural-stability modification. In this paper, a structure-based statistical thermodynamic approach is presented and used to predict the propagation of the stabilization effects triggered by the binding of the monoclonal antibody D1.3 to hen egg white lysozyme, previously, Williams et al. [Williams, D. C., Benjamin, D. C,, Poljak, R. J, & Rule, GI S. (1996) J. Mol. Biol, 257, 866-876] showed that the binding of this antibody affects the stability of hen egg white lysozyme and that the binding effects propagate to a selected number of residues at remote locations from the binding epitope, In this paper, me show that this phenomenon can be predicted from structure. The formalism presented here permits the identification of the structural path followed by cooperative interactions that originate at the binding site. It is shown that an important condition for the propagation of binding effects to distal regions is the presence of a significant fraction of residues with low structural stability in the uncomplexed binding site. A survey of protein structures indicates that many binding sites have a dual character and are defined by regions of high and low structural stabilities. The low-stability regions might be involved in the transmission of binding information to other regions in the protein.