Structural insights into microneme protein assembly reveal a new mode of EGF domain recognition.
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.
Sawmynaden
Kovilen
K
Division of Molecular Biosciences, Imperial College London, Exhibition Road, South Kensington Campus, London SW7 2AZ, UK.
Saouros
Savvas
S
Friedrich
Nikolas
N
Marchant
Jan
J
Simpson
Peter
P
Bleijlevens
Boris
B
Blackman
Michael J
MJ
Soldati-Favre
Dominique
D
Matthews
Stephen
S
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*
D015815:Cell Adhesion Molecules; C105877:MIC1 protein, Toxoplasma gondii; C512738:MIC6 protein, Toxoplasma gondii; D015800:Protozoan Proteins; D011991:Receptors, Virus