PLoS ONE (Jan 2012)

Antibody recognition of cancer-related gangliosides and their mimics investigated using in silico site mapping.

  • Mark Agostino,
  • Elizabeth Yuriev,
  • Paul A Ramsland

DOI
https://doi.org/10.1371/journal.pone.0035457
Journal volume & issue
Vol. 7, no. 4
p. e35457

Abstract

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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.