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Science 333 (6041): 463-467

Copyright © 2011 by the American Association for the Advancement of Science

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

Michelle L. Tonkin,1,* Magali Roques,2,* Mauld H. Lamarque,2 Martine Pugnière,3 Dominique Douguet,4 Joanna Crawford,1 Maryse Lebrun,2,*,{dagger} Martin J. Boulanger1,*,{dagger}

Abstract: 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.

1 Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8W 3P6, Canada.
2 UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
3 Institut de Recherche en Cancerologie de Montpellier, INSERM U896, 34298 Montpellier, France.
4 CNRS UMR6097-Université Nice-Sophia Antipolis 660, 06560 Valbonne, France.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: mboulang{at}uvic.ca (M.J.B.); mylebrun{at}univ-montp2.fr (M.L.)


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