Characterization of a diagnostic Fab fragment binding trimeric Lewis X

Lewis X trisaccharides normally function as essential cell–cell interaction mediators. However, oligomers of Lewis X trisaccharides expressed by the parasite Schistosoma mansoni seem to be related to its evasion of the immune response of its human host. Here we show that monoclonal antibody 54‐5C10‐...

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Veröffentlicht in:Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2009-08, Vol.76 (2), p.439-447
Hauptverfasser: de Geus, Daniël C., van Roon, Anne-Marie M., Thomassen, Ellen A. J., Hokke, Cornelis H., Deelder, André M., Abrahams, Jan Pieter
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Sprache:eng
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Zusammenfassung:Lewis X trisaccharides normally function as essential cell–cell interaction mediators. However, oligomers of Lewis X trisaccharides expressed by the parasite Schistosoma mansoni seem to be related to its evasion of the immune response of its human host. Here we show that monoclonal antibody 54‐5C10‐A, which is used to diagnose schistosomiasis in humans, interacts with oligomers of at least three Lewis X trisaccharides, but not with monomeric Lewis X. We describe the sequence and the 2.5 Å crystal structure of its Fab fragment and infer a possible mode of binding of the polymeric Lewis X from docking studies. Our studies indicate a radically different mode of binding compared to Fab 291‐2G3‐A, which is specific for monomeric Lewis X, thus providing a structural explanation of the diagnostic success of 54‐5C10‐A. Proteins 2009. © 2008 Wiley‐Liss, Inc.
ISSN:0887-3585
1097-0134
DOI:10.1002/prot.22356