Atomic resolution insight into host cell recognition by Toxoplasma gondii

Blumenschein, Tharin M. A. ORCID: https://orcid.org/0000-0002-4932-5178, Friedrich, Nikolas, Childs, Robert A, Saouros, Savvas, Carpenter, Elisabeth P, Campanero-Rhodes, Maria A, Simpson, Peter, Chai, Wengang, Koutroukides, Theodoros, Blackman, Michael J, Feizi, Ten, Soldati-Favre, Dominique and Matthews, Stephen (2007) Atomic resolution insight into host cell recognition by Toxoplasma gondii. The EMBO Journal, 26 (11). pp. 2808-2820. ISSN 1460-2075

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Abstract

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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Chemistry (former - to 2024)
UEA Research Groups: Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Faculty of Science > Research Groups > Biophysical Chemistry (former - to 2017)
Depositing User: Rachel Smith
Date Deposited: 15 Feb 2011 12:34
Last Modified: 24 Sep 2024 09:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/21374
DOI: 10.1038/sj.emboj.7601704

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