CONTINUOUS AND DISCONTINUOUS PROTEIN ANTIGENIC DETERMINANTS
CONTINUOUS AND DISCONTINUOUS PROTEIN ANTIGENIC DETERMINANTS
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DOI：
10.1038/322747a0
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发表时间：
1986-08-21
期刊：
影响因子：
64.8
通讯作者：
THORNTON, JM
中科院分区：
文献类型：
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作者：
BARLOW, DJ;EDWARDS, MS;THORNTON, JM
蛋白质抗原决定簇分为连续决定簇和不连续决定簇。连续决定簇由多肽序列中局部残基组成，而不连续决定簇由来自序列不同部分的残基组成，这些残基通过蛋白质折叠到其天然结构而聚集在一起。使用与蛋白质-抗体复合体形成竞争的多肽片段或可用于产生与天然蛋白质交叉反应的抗体的多肽来搜索蛋白质决定因素，仅限于对连续决定因素的模拟。然而，最近的实验2，3表明，大多数决定因素是不连续的。我们现在证明，通过考虑蛋白质表面，如果蛋白质和抗体之间的识别区与溶菌酶-抗体复合体4的识别区具有相同的尺寸，那么蛋白质的表面将没有一个是连续的。我们认为所有的决定因素在某种程度上都是不连续的，并且交叉反应的多肽只模仿‘主要’相互作用部位。此外，我们发现蛋白质表面最连续的部分主要落在环状和/或突出区域。这就解释了为什么诸如亲水性、可获得性、流动性和突出度等数量可以用来预测多肽的哪些部分提供“最好的”抗原肽。
Protein antigenic determinants have been classified as continuous or discontinuous1,2. The continuous determinants are composed of residues which are local in the polypeptide sequence, while discontinuous determinants consist of residues from different parts of the sequence, brought together by the folding of the protein to its native structure. Searches made for protein determinants using peptide fragments which compete with protein–antibody complex formation, or peptides that can be used to raise antibodies which crossreact with the native protein, are limited to the simulation of continuous determinants. However, recent experiments2,3suggest that most determinants are discontinuous. We now show, by consideration of protein surfaces, that if the recognition zone between a protein and antibody has the same dimensions as those found for the lysozyme–antibody complex4, none of the protein's surface will be ‘continuous’. We suggest that all determinants are discontinuous to some extent, and that crossreacting peptides mimic only the ‘primary’ interaction site. In addition, we show that the parts of a protein's surface which are most continuous fall predominantly in the loops and/or protruding regions. This explains why quantities such as hydrophilicity5, accessibility6, mobility7and protrusion8can be used to predict which parts of a polypeptide provide the ‘best’ antigenic peptides.