ANTIGENIC DETERMINANTS IN PROTEINS COINCIDE WITH SURFACE REGIONS ACCESSIBLE TO LARGE PROBES (ANTIBODY DOMAINS)
ANTIGENIC DETERMINANTS IN PROTEINS COINCIDE WITH SURFACE REGIONS ACCESSIBLE TO LARGE PROBES (ANTIBODY DOMAINS)
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DOI：
10.1073/pnas.83.2.226
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发表时间：
1986-01-01
影响因子：
11.1
通讯作者：
ROSE, GD
中科院分区：
文献类型：
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作者：
NOVOTNY, J;HANDSCHUMACHER, M;ROSE, GD
我们评估了与大(1纳米半径)球形探针接触的蛋白质的表面积。这种球体的大小与含有抗原结合部位的抗体区域相当。我们发现，所有已报道的抗原点都对应于一个大球体特别容易接近的片段。在溶剂可接触(小探针)表面的等高线图中，抗原部位也是最明显的暴露区域(山丘和山脊)。在肌红蛋白和细胞色素c中，几乎所有的范德华表面都可以被大探针接触到，因此具有潜在的抗原性；在肌红蛋白中，明显的大探针不能到达的、非抗原性的表面区是明显的。肌红蛋白、溶菌酶和细胞色素c的大球可及性和抗原性之间的相关性似乎比报道的抗原性和节段灵活性之间的相关性更好；也就是说，表面坚硬的区域通常包含抗原表位，而分子的一些柔性部分似乎不具有抗原性。我们认为，某些多肽链片段具有抗原性的主要原因是它们特殊的表面暴露，使它们很容易与抗原结合部位接触。这些节段的暴露经常导致高流动性，从而导致报道的抗原性和节段灵活性之间的相关性。
We evaluated surface areas on proteins that would be accessible to contacts with large (1-nm radius) spherical probes. Such spheres are comparable in size to antibody domains that contain antigen-combining sites. We found that all the reported antigenic sites correspond to segments particularly accessible to a large sphere. The antigenic sites were also evident as the most prominently exposed regions (hills and ridges) in contour maps of the solvent-accessible (small-probe) surface. In myoglobin and cytochrome c, virtually all of the van der Waals surface is accessible to the large probe and therefore potentially antigenic; in myohemerythrin, distinct large-probe-inacessible, and nonantigenic, surface regions are apparent. The correlation between large-sphere-accessibility and antigenicity in myoglobin, lysozyme, and cytochrome c appears to be better than that reported to exist between antigenicity and segmental flexibility; that is, surface regions that are rigid often consitute antigenic epitopes, whereas some of the flexible parts of the molecules do not appear antigenic. We propose that the primary reason why certain polypeptide-chain segments are antigenic is their exceptional surface exposure, making them readily avaiable for contacts with antigen-combining sites. Exposure of these segments frequently results in high mobility and, in consequence, to the reported correlation between antigenicity and segmental flexibility.