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Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii

Garnett, James A.; Liu, Yan; Leon, Ester; Allman, Sarah; Friedrich, Nikolas; Saouros, Savvas; Curry, Stephen; Soldati-Favre, Dominique; Davis, Benjamin G.; Feizi, Ten and Matthews, Stephen (2009). Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii. Protein Science, 18(9) pp. 1935–1947.

DOI (Digital Object Identifier) Link: https://doi.org/10.1002/pro.204
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Abstract

The intracellular protozoan Toxoplasma gondii is among the most widespread parasites. The broad host cell range of the parasite can be explained by carbohydrate microarray screening analyses that have demonstrated the ability of the T. gondii adhesive protein, TgMIC1, to bind to a wide spectrum of sialyl oligosaccharide ligands. Here, we investigate by further microarray analyses in a dose-response format the differential binding of TgMIC1 to 2-3- and 2-6-linked sialyl carbohydrates. Interestingly, two novel synthetic fluorinated analogs of 3'SiaLacNAc1-4 and 3'SiaLacNAc1-3 were identified as highly potent ligands. To understand the structural basis of the carbohydrate binding specificity of TgMIC1, we have determined the crystal structures of TgMIC1 micronemal adhesive repeat (MAR)-region (TgMIC1-MARR) in complex with five sialyl-N-acetyllactosamine analogs. These crystal structures have revealed a specific, water-mediated hydrogen bond network that accounts for the preferential binding of TgMIC1-MARR to arrayed 2-3-linked sialyl oligosaccharides and the high potency of the fluorinated analogs. Furthermore, we provide strong evidence for the first observation of a C--F...H--O hydrogen bond within a lectin-carbohydrate complex. Finally, detailed comparison with other oligosaccharide-protein complexes in the Protein Data Bank (PDB) reveals a new family of sialic-acid binding sites from lectins in parasites, bacteria, and viruses.

Item Type: Journal Item
Copyright Holders: 2009 The Protein Society
ISSN: 1469-896X
Keywords: Toxoplasma gondii; sialic acid; crystal structure; MIC1; microneme proteins; carbohydrate microarray
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 38121
Depositing User: Sarah Allman
Date Deposited: 07 Aug 2013 12:17
Last Modified: 07 Dec 2018 10:17
URI: http://oro.open.ac.uk/id/eprint/38121
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