title: Structural insights into microneme protein assembly reveal a new mode of EGF domain recognition.
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. Adhesive complexes composed of microneme proteins (MICs) are secreted onto the parasite surface from intracellular stores and fulfil crucial roles in host-cell recognition, attachment and penetration. Here, we report the high-resolution solution structure of a complex between two crucial MICs, TgMIC6 and TgMIC1. Furthermore, we identify two analogous interaction sites within separate epidermal growth factor-like (EGF) domains of TgMIC6-EGF2 and EGF3-and confirm that both interactions are functional for the recognition of host cell receptor in the parasite, using immunofluorescence and invasion assays. The nature of this new mode of recognition of the EGF domain and its abundance in apicomplexan surface proteins suggest a more generalized means of constructing functional assemblies by using EGF domains with highly specific receptor-binding properties.
authors.affiliation: Division of Molecular Biosciences, Imperial College London, Exhibition Road, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Kovilen
authors.initials: K
authors.lastname: Sawmynaden
authors.forename: Savvas
authors.initials: S
authors.lastname: Saouros
authors.forename: Nikolas
authors.initials: N
authors.lastname: Friedrich
authors.forename: Jan
authors.initials: J
authors.lastname: Marchant
authors.forename: Peter
authors.initials: P
authors.lastname: Simpson
authors.forename: Boris
authors.initials: B
authors.lastname: Bleijlevens
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blackman
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D054730:Protein Interaction Domains and Motifs; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D014122:Toxoplasma / Q000737:chemistry*
chemical_list: D015815:Cell Adhesion Molecules; C105877:MIC1 protein, Toxoplasma gondii; C512738:MIC6 protein, Toxoplasma gondii; D015800:Protozoan Proteins; D011991:Receptors, Virus