Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping

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 a...

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Main Authors: Agostino, Mark, Yuriev, E., Ramsland, Paul
Format: Journal Article
Published: Public Library of Science 2012
Online Access:http://hdl.handle.net/20.500.11937/39513
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author Agostino, Mark
Yuriev, E.
Ramsland, Paul
author_facet Agostino, Mark
Yuriev, E.
Ramsland, Paul
author_sort Agostino, Mark
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-395132017-09-13T14:26:50Z Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping Agostino, Mark Yuriev, E. Ramsland, Paul 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/39513 10.1371/journal.pone.0035457 Public Library of Science fulltext
spellingShingle Agostino, Mark
Yuriev, E.
Ramsland, Paul
Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title_full Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title_fullStr Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title_full_unstemmed Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title_short Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping
title_sort antibody recognition of cancer-related gangliosides and their mimics investigated using in silico site mapping
url http://hdl.handle.net/20.500.11937/39513