| Structural highlights
3f5e is a 1 chain structure with sequence from Toxoplasma gondii RH. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
MIC1_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 PubMed
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'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
- ↑ Lourenco EV, Pereira SR, Faca VM, Coelho-Castelo AA, Mineo JR, Roque-Barreira MC, Greene LJ, Panunto-Castelo A. Toxoplasma gondii micronemal protein MIC1 is a lactose-binding lectin. Glycobiology. 2001 Jul;11(7):541-7. PMID:11447133
- ↑ Reiss M, Viebig N, Brecht S, Fourmaux MN, Soete M, Di Cristina M, Dubremetz JF, Soldati D. Identification and characterization of an escorter for two secretory adhesins in Toxoplasma gondii. J Cell Biol. 2001 Feb 5;152(3):563-78. PMID:11157983
- ↑ Saouros S, Edwards-Jones B, Reiss M, Sawmynaden K, Cota E, Simpson P, Dowse TJ, Jakle U, Ramboarina S, Shivarattan T, Matthews S, Soldati-Favre D. A novel galectin-like domain from Toxoplasma gondii micronemal protein 1 assists the folding, assembly, and transport of a cell adhesion complex. J Biol Chem. 2005 Nov 18;280(46):38583-91. Epub 2005 Sep 15. PMID:16166092 doi:C500365200
- ↑ Blumenschein TM, Friedrich N, Childs RA, Saouros S, Carpenter EP, Campanero-Rhodes MA, Simpson P, Chai W, Koutroukides T, Blackman MJ, Feizi T, Soldati-Favre D, Matthews S. Atomic resolution insight into host cell recognition by Toxoplasma gondii. EMBO J. 2007 Jun 6;26(11):2808-20. Epub 2007 May 10. PMID:17491595
- ↑ Fourmaux MN, Achbarou A, Mercereau-Puijalon O, Biderre C, Briche I, Loyens A, Odberg-Ferragut C, Camus D, Dubremetz JF. The MIC1 microneme protein of Toxoplasma gondii contains a duplicated receptor-like domain and binds to host cell surface. Mol Biochem Parasitol. 1996 Dec 20;83(2):201-10. PMID:9027753
- ↑ Garnett JA, Liu Y, Leon E, Allman S, Friedrich N, Saouros S, Curry S, Soldati-Favre D, Davis B, Feizi T, Matthews S. Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii. Protein Sci. 2009 Jul 10. PMID:19593815 doi:10.1002/pro.204
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