Host Cell Invasion by Apicomplexan Parasites: Insights from the Co-Structure of AMA1 with a RON2 Peptide

• Published in: Science (American Association for the Advancement of Science) 2011-07, Vol.333 (6041), p.463-467
• Main Authors: Tonkin, Michelle L., Roques, Magali, Lamarque, Mauld H., Pugnière, Martine, Douguet, Dominique, Crawford, Joanna, Lebrun, Maryse, Boulanger, Martin J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Antibodies, Monoclonal - immunology; Antibodies, Protozoan - immunology; Antigens; Antigens, Protozoan - chemistry; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Protozoan - metabolism; Assembly; Bioinformatics; Biological and medical sciences; Cell membranes; Chemical Sciences; Cheminformatics; Computer Science; Crystalline structure; Fundamental and applied biological sciences. Psychology; Host-Parasite Interactions; Hydrophobic and Hydrophilic Interactions; Life Sciences; Medicinal Chemistry; Membrane Proteins - chemistry; Membrane Proteins - immunology; Membrane Proteins - metabolism; Membranes; Models, Molecular; Molecular biophysics; Molecular Sequence Data; Mutagenesis; Necks; Obligate parasites; Parasite hosts; Parasites; Parasitism; Pathogens; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptides; Pharmaceutical sciences; Plasmodium; Plasmodium falciparum - chemistry; Plasmodium falciparum - metabolism; Plasmodium falciparum - pathogenicity; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Protozoan Proteins - chemistry; Protozoan Proteins - immunology; Protozoan Proteins - metabolism; Receptors; Scientific Concepts; Structure in molecular biology; Surface area; Toxoplasma - chemistry; Toxoplasma - metabolism; Toxoplasma - pathogenicity; Toxoplasma - ultrastructure; Toxoplasma gondii
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1204988

Apicomplexan parasites such as Toxoplasma gondii and Plasmodium species actively invade host cells through a moving junction (MJ) complex assembled at the parasite—host cell interface. MJ assembly is initiated by injection of parasite rhoptry neck proteins (RONs) into the host cell, where RON2 spans the membrane and functions as a receptor for apical membrane antigen 1 (AMA1) on the parasite. We have determined the structure of TgAMA1 complexed with a RON2 peptide at 1.95 angstrom resolution. A stepwise assembly mechanism results in an extensive buried surface area, enabling the MJ complex to resist the mechanical forces encountered during host cell invasion. Besides providing insights into host cell invasion by apicomplexan parasites, the structure offers a basis for designing therapeutics targeting these global pathogens.