TY - JOUR
T1 - Atomic resolution insight into host cell recognition by Toxoplasma gondii
AU - Blumenschein, Tharin M. A.
AU - Friedrich, Nikolas
AU - Childs, Robert A
AU - Saouros, Savvas
AU - Carpenter, Elisabeth P
AU - Campanero-Rhodes, Maria A
AU - Simpson, Peter
AU - Chai, Wengang
AU - Koutroukides, Theodoros
AU - Blackman, Michael J
AU - Feizi, Ten
AU - Soldati-Favre, Dominique
AU - Matthews, Stephen
PY - 2007/5/10
Y1 - 2007/5/10
N2 - The obligate intracellular parasite Toxoplasma gondii, a member of the phylum Apicomplexa that includes Plasmodium spp., is one of the most widespread parasites and the causative agent of toxoplasmosis. Micronemal proteins (MICs) are released onto the parasite surface just before invasion of host cells and play important roles in host cell recognition, attachment and penetration. Here, we report the atomic structure for a key MIC, TgMIC1, and reveal a novel cell-binding motif called the microneme adhesive repeat (MAR). Using glycoarray analyses, we identified a novel interaction with sialylated oligosaccharides that resolves several prevailing misconceptions concerning TgMIC1. Structural studies of various complexes between TgMIC1 and sialylated oligosaccharides provide high-resolution insights into the recognition of sialylated oligosaccharides by a parasite surface protein. We observe that MAR domains exist in tandem repeats, which provide a highly specialized structure for glycan discrimination. Our work uncovers new features of parasite–receptor interactions at the early stages of host cell invasion, which will assist the design of new therapeutic strategies.
AB - The obligate intracellular parasite Toxoplasma gondii, a member of the phylum Apicomplexa that includes Plasmodium spp., is one of the most widespread parasites and the causative agent of toxoplasmosis. Micronemal proteins (MICs) are released onto the parasite surface just before invasion of host cells and play important roles in host cell recognition, attachment and penetration. Here, we report the atomic structure for a key MIC, TgMIC1, and reveal a novel cell-binding motif called the microneme adhesive repeat (MAR). Using glycoarray analyses, we identified a novel interaction with sialylated oligosaccharides that resolves several prevailing misconceptions concerning TgMIC1. Structural studies of various complexes between TgMIC1 and sialylated oligosaccharides provide high-resolution insights into the recognition of sialylated oligosaccharides by a parasite surface protein. We observe that MAR domains exist in tandem repeats, which provide a highly specialized structure for glycan discrimination. Our work uncovers new features of parasite–receptor interactions at the early stages of host cell invasion, which will assist the design of new therapeutic strategies.
U2 - 10.1038/sj.emboj.7601704
DO - 10.1038/sj.emboj.7601704
M3 - Article
VL - 26
SP - 2808
EP - 2820
JO - The EMBO Journal
JF - The EMBO Journal
SN - 0261-4189
IS - 11
ER -