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  • The EMBO Journal (2007) 26, 2808 - 2820
  • doi:10.1038/sj.emboj.7601704

Published online: 10 May 2007

Atomic resolution insight into host cell recognition by Toxoplasma gondii

Tharin MA Blumenschein1,a, Nikolas Friedrich2,a, Robert A Childs3, Savvas Saouros1, Elisabeth P Carpenter1, Maria A Campanero-Rhodes3, Peter Simpson1, Wengang Chai3, Theodoros Koutroukides4, Michael J Blackman5, Ten Feizi3, Dominique Soldati-Favre2 and Stephen Matthews1

  1. Division of Molecular Biosciences, Imperial College London, London, UK
  2. Department of Microbiology and Genetics, Faculty of Medicine, University of Geneva CMU, Geneva, Switzerland
  3. Glycosciences Laboratory, Division of Medicine, Imperial College London, Middlesex, UK
  4. Medical Science Division, Fox Chase Cancer Centre, Philadelphia, PA, USA
  5. Division of Parasitology, National Institute for Medical Research, London, UK

Correspondence to:

Stephen Matthews, Division of Molecular Biosciences, Imperial College of Science, Technology and Medicine, South Kensington Campus, London SW7 2AZ, UK. Tel.: +44 207 594 5315; Fax: +44 207 594 5207; E-mail: s.j.matthews@imperial.ac.uk

aThese authors contributed equally to this work

Received 30 November 2006; Accepted 4 April 2007

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.

  • Keywords:

    • carbohydrate microarray,
    • crystal structure,
    • micronemal proteins,
    • sialic acid,
    • T. gondii