A novel galectin-like domain from Toxoplasma gondii micronemal protein 1 assists the folding, assembly, and transport of a cell adhesion complex.
Immediately prior to invasion Toxoplasma gondii tachyzoites release a large number of micronemal proteins (TgMICs) that participate in host cell attachment and penetration. The TgMIC4-MIC1-MIC6 complex was the first to be identified in T. gondii and has been recently shown to be critical in invasion. This study establishes that the N-terminal thrombospondin type I repeat-like domains (TSR1-like) from TgMIC1 function as an independent adhesin as well as promoting association with TgMIC4. Using the newly solved three-dimensional structure of the C-terminal domain of TgMIC1 we have identified a novel Galectin-like fold that does not possess carbohydrate binding properties and redefines the architecture of TgMIC1. Instead, the TgMIC1 Galectin-like domain interacts and stabilizes TgMIC6, which provides the basis for a highly specific quality control mechanism for successful exit from the early secretory compartments and for subsequent trafficking of the complex to the micronemes.
Saouros
Savvas
S
Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
Edwards-Jones
Bryn
B
Reiss
Matthias
M
Sawmynaden
Kovilen
K
Cota
Ernesto
E
Simpson
Peter
P
Dowse
Timothy J
TJ
Jäkle
Ursula
U
Ramboarina
Stephanie
S
Shivarattan
Tara
T
Matthews
Stephen
S
Soldati-Favre
Dominique
D
D000818:Animals; D015153:Blotting, Western; D002241:Carbohydrates / Q000737:chemistry; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D037161:Galectins / Q000737:chemistry*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008968:Molecular Conformation; D009361:Neoplasm Invasiveness; D010843:Pichia / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D019699:Thrombospondins / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism*; D014162:Transfection
D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D037161:Galectins; C105877:MIC1 protein, Toxoplasma gondii; C428323:MIC4 protein, Toxoplasma gondii; D015800:Protozoan Proteins; D019699:Thrombospondins