title: Galactose recognition by the apicomplexan parasite Toxoplasma gondii.
abstract: Toxosplasma gondii is the model parasite of the phylum Apicomplexa, which contains numerous obligate intracellular parasites of medical and veterinary importance, including Eimeria, Sarcocystis, Cryptosporidium, Cyclospora, and Plasmodium species. Members of this phylum actively enter host cells by a multistep process with the help of microneme protein (MIC) complexes that play important roles in motility, host cell attachment, moving junction formation, and invasion. T. gondii (Tg)MIC1-4-6 complex is the most extensively investigated microneme complex, which contributes to host cell recognition and attachment via the action of TgMIC1, a sialic acid-binding adhesin. Here, we report the structure of TgMIC4 and reveal its carbohydrate-binding specificity to a variety of galactose-containing carbohydrate ligands. The lectin is composed of six apple domains in which the fifth domain displays a potent galactose-binding activity, and which is cleaved from the complex during parasite invasion. We propose that galactose recognition by TgMIC4 may compromise host protection from galectin-mediated activation of the host immune system.
authors.affiliation: Division of Molecular Biosciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: Marchant
authors.forename: Ben
authors.initials: B
authors.lastname: Cowper
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Livia
authors.initials: L
authors.lastname: Lai
authors.forename: Camila
authors.initials: C
authors.lastname: Pinzan
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Marq
authors.forename: Nikolas
authors.initials: N
authors.lastname: Friedrich
authors.forename: Kovilen
authors.initials: K
authors.lastname: Sawmynaden
authors.forename: Lloyd
authors.initials: L
authors.lastname: Liew
authors.forename: Wengang
authors.initials: W
authors.lastname: Chai
authors.forename: Robert A
authors.initials: RA
authors.lastname: Childs
authors.forename: Savvas
authors.initials: S
authors.lastname: Saouros
authors.forename: Peter
authors.initials: P
authors.lastname: Simpson
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Roque Barreira
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D005690:Galactose / Q000276:immunology / Q000378:metabolism*; D037161:Galectins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins; D014122:Toxoplasma / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D037161:Galectins; C428323:MIC4 protein, Toxoplasma gondii; D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D005690:Galactose