Characterization of a diagnostic Fab fragment binding trimeric Lewis X.

Abstract

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 A 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.

• Authors: Daniël C de Geus, Anne-Marie M van Roon, Ellen A J Thomassen, Cornelis H Hokke, André M Deelder, Jan Pieter Abrahams
• Journal: Proteins (Proteins) Vol. 76 Issue 2 Pg. 439-47 (Aug 01 2009) ISSN: 1097-0134 [Electronic] United States
• PMID: 19173313 (Publication Type: Journal Article)
• Copyright: 2008 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin Fab Fragments
• Lewis X Antigen
• Trisaccharides
• galactosyl-(1,4)-fucopyranosyl-(1,3)-N-acetylglucosamine

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Monoclonal (chemistry, immunology)
• Binding Sites
• Crystallography, X-Ray
• Humans
• Immunoglobulin Fab Fragments (chemistry, immunology)
• Lewis X Antigen (analogs & derivatives)
• Mice
• Models, Molecular
• Molecular Sequence Data
• Protein Conformation
• Sequence Alignment
• Surface Plasmon Resonance
• Trisaccharides (chemistry, immunology)