Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens
Carbohydrate–antibody interactions mediate many cellular processes and immune responses. Carbohydrates expressed on the surface of cells serve as recognition elements for particular cell types, for example, in the ABO(H) blood group system. Antibodies that recognize host-incompatible ABO(H) system a...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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John Wiley and Sons, Inc.
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/18119 |
| _version_ | 1848749653280948224 |
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| author | Agostino, Mark Sandrin, M. Thompson, P. Ramsland, P. Yuriev, E. |
| author_facet | Agostino, Mark Sandrin, M. Thompson, P. Ramsland, P. Yuriev, E. |
| author_sort | Agostino, Mark |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Carbohydrate–antibody interactions mediate many cellular processes and immune responses. Carbohydrates expressed on the surface of cells serve as recognition elements for particular cell types, for example, in the ABO(H) blood group system. Antibodies that recognize host-incompatible ABO(H) system antigens exist in the bloodstream of all individuals (except AB individuals), preventing bloodtransfusion and organ transplantation between incompatible donors and recipients. A similar barrier exists for cross-species transplantation (xenotransplantation), in particular for pig-to-human transplantation. All humans express antibodies against the major carbohydrate xenoantigen, Galα(1,3)Gal (αGal), preventing successful xenotransplantation. Although antibody binding sites are precisely organized so as to selectively bind a specific antigen, many antibodies recognize molecules other than their native antigen. A range of peptides have been identified that can mimic carbohydrates and inhibit anti-αGal antibodies. However, the structural basis of how the peptides achieved this was not known. Previously, we developed an in silico method which we used to investigate carbohydrate recognition by a panel of anti-αGal antibodies. The method involves molecular docking of carbohydrates to antibodies and uses the docked carbohydrate poses to generate maps of the antibody binding sites in terms of prevalent hydrogen bonding and van der Waals interactions. We have applied this method to investigate peptide recognition by the anti-αGal antibodies. It was found that the site maps of the peptides and the carbohydrates were similar, indicating that the peptides interact with the same residues as those involved in carbohydrate recognition. This study demonstrates the potential for “design by mapping” of anti-carbohydrate antibody inhibitors. |
| first_indexed | 2025-11-14T07:24:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-18119 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:24:21Z |
| publishDate | 2011 |
| publisher | John Wiley and Sons, Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-181192017-09-13T13:47:28Z Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens Agostino, Mark Sandrin, M. Thompson, P. Ramsland, P. Yuriev, E. docking carbohydrate antibody peptide mimicry Carbohydrate–antibody interactions mediate many cellular processes and immune responses. Carbohydrates expressed on the surface of cells serve as recognition elements for particular cell types, for example, in the ABO(H) blood group system. Antibodies that recognize host-incompatible ABO(H) system antigens exist in the bloodstream of all individuals (except AB individuals), preventing bloodtransfusion and organ transplantation between incompatible donors and recipients. A similar barrier exists for cross-species transplantation (xenotransplantation), in particular for pig-to-human transplantation. All humans express antibodies against the major carbohydrate xenoantigen, Galα(1,3)Gal (αGal), preventing successful xenotransplantation. Although antibody binding sites are precisely organized so as to selectively bind a specific antigen, many antibodies recognize molecules other than their native antigen. A range of peptides have been identified that can mimic carbohydrates and inhibit anti-αGal antibodies. However, the structural basis of how the peptides achieved this was not known. Previously, we developed an in silico method which we used to investigate carbohydrate recognition by a panel of anti-αGal antibodies. The method involves molecular docking of carbohydrates to antibodies and uses the docked carbohydrate poses to generate maps of the antibody binding sites in terms of prevalent hydrogen bonding and van der Waals interactions. We have applied this method to investigate peptide recognition by the anti-αGal antibodies. It was found that the site maps of the peptides and the carbohydrates were similar, indicating that the peptides interact with the same residues as those involved in carbohydrate recognition. This study demonstrates the potential for “design by mapping” of anti-carbohydrate antibody inhibitors. 2011 Journal Article http://hdl.handle.net/20.500.11937/18119 10.1002/bip.21427 John Wiley and Sons, Inc. restricted |
| spellingShingle | docking carbohydrate antibody peptide mimicry Agostino, Mark Sandrin, M. Thompson, P. Ramsland, P. Yuriev, E. Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title | Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title_full | Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title_fullStr | Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title_full_unstemmed | Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title_short | Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| title_sort | peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens |
| topic | docking carbohydrate antibody peptide mimicry |
| url | http://hdl.handle.net/20.500.11937/18119 |