3f5a
Crystal structure of Toxoplasma gondii micronemal protein 1 bound to 3'SiaLacNAc1-3
Structural highlights
FunctionMIC1_TOXGO Adhesin. Required for attachment of the parasite to the host cell prior to invasion. Ensures correct folding of MIC6 and transport of the MIC6-MIC1-MIC4 complex into the micronemes.[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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'siaLacNAc(1-4) and 3'siaLacNAc(1-3) 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 the 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. Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii.,Garnett JA, Liu Y, Leon E, Allman S, Friedrich N, Saouros S, Curry S, Soldati-Favre D, Davis B, Feizi T, Matthews S Protein Sci. 2009 Jul 10. PMID:19593815[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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