Mapping epitope structure and activity: From one-dimensional prediction to four-dimensional description of antigenic specificity
Mapping epitope structure and activity: From one-dimensional prediction to four-dimensional description of antigenic specificity
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DOI：
10.1006/meth.1996.0054
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发表时间：
1996-01-01
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影响因子：
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通讯作者：
Van Regenmortal, Marc H. V.
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文献类型：
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作者：
Van Regenmortal, Marc H. V.
近年来，主要通过对与单克隆抗体复合的蛋白质和肽进行 X 射线晶体学研究，我们对抗原特异性的了解大大增加。然而，我们预测蛋白质中抗原位点位置的能力仍然有限，部分原因是预测算法将表位的复杂性降低为一维线性肽模型。表位和互补位是可通过其相互互补性和适应潜力以及其活性来定义的关系实体。对抗原特异性的完整解释需要整合结构和结合活性数据，而这只能通过时空四维分析来实现。在抗原抗体互补性分析中未能包括第四个维度，即时间，相当于将蛋白质视为刚体，并忽略了两个伙伴相互作用时发生的相互适应。将四维蛋白质系统简化为三维或二维表示不可避免地扭曲了我们对表位动态性质的看法。
Our knowledge of antigenic specificity has greatly increased in recent years mainly through X-ray crystallographic studies of proteins and peptides complexed with monoclonal antibodies. However, our ability to predict the location of antigenic sites in proteins remains limited partly because prediction algorithms reduce the complexity of epitopes to one-dimensional, linear peptide models. Epitopes and paratopes are relational entities definable by their mutual complementarity and adaptation potential as well as by their activity. A complete account of antigenic specificity demands the integration of both structural and binding activity data that can be achieved only through a spatiotemporal four-dimensional analysis. Failure to include the fourth dimension, i.e., time, in the analysis of antigen-antibody complementarity amounts to considering proteins as rigid bodies and ignores the mutual adaptation that occurs when the two partners interact. Reducing four-dimensional protein systems to three-dimensional or two-dimensional representations inevitably distorts our perception of the dynamic nature of epitopes.