Antibody recognition of cancer-related gangliosides and their mimics investigated using in silico site mapping.
Antibody recognition of cancer-related gangliosides and their mimics investigated using in silico site mapping.
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DOI：
10.1371/journal.pone.0035457
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ramsland PA
中科院分区：
文献类型：
--
作者：
Agostino M;Yuriev E;Ramsland PA
修饰神经节苷在某些类型的癌症中可能过表达，因此，它们被认为是癌症免疫治疗的一个有价值的靶点。由于这些配体的大尺寸和高灵活性，它们与抗体相互作用的结构知识目前是有限的。在这项研究中，我们应用我们先前开发的位点定位技术来研究抗神经节苷脂抗体对癌症相关神经节苷脂的识别。结果显示，在研究的四种抗体中存在潜在的神经节苷脂结合基序，提示抗神经节苷脂免疫反应中可能存在结构趋同。识别神经节苷脂类肽的结构基础也进行了研究，使用位点定位和比较神经节苷脂识别。这些肽通过与许多与同源碳水化合物表位相同的结合位点残基相互作用，显示出作为神经节苷的结构模拟物。这些研究为研究碳水化合物免疫模拟的结构基础提供了重要线索。
Modified gangliosides may be overexpressed in certain types of cancer, thus, they are considered a valuable target in cancer immunotherapy. Structural knowledge of their interaction with antibodies is currently limited, due to the large size and high flexibility of these ligands. In this study, we apply our previously developed site mapping technique to investigate the recognition of cancer-related gangliosides by anti-ganglioside antibodies. The results reveal a potential ganglioside-binding motif in the four antibodies studied, suggesting the possibility of structural convergence in the anti-ganglioside immune response. The structural basis of the recognition of ganglioside-mimetic peptides is also investigated using site mapping and compared to ganglioside recognition. The peptides are shown to act as structural mimics of gangliosides by interacting with many of the same binding site residues as the cognate carbohydrate epitopes. These studies provide important clues as to the structural basis of immunological mimicry of carbohydrates.
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影响因子：
5.6
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
影响因子：
3.6
作者：
Föster-Waldl, E;Riemer, AB;Jensen-Jarolim, E
通讯作者：
Jensen-Jarolim, E
影响因子：
5.6
作者：
AlLazikani, B;Lesk, AM;Chothia, C
通讯作者：
Chothia, C
影响因子：
2.9
作者：
Agostino, Mark;Sandrin, Mauro S.;Yuriev, Elizabeth
通讯作者：
Yuriev, Elizabeth
影响因子：
4.3
作者：
Agostino, Mark;Sandrin, Mauro S.;Ramsland, Paul A.
通讯作者：
Ramsland, Paul A.