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Apicomplexan parasites are a group of intracellular parasites that can live in various animal hosts, including humans, where they can cause serious diseases such as malaria and toxoplasmosis. However, entering a host cell is not an easy undertaking for the parasite and resembles boarding a well-fortified galley. For this purpose they are equipped with a unique grappling device known as a ‘moving junction’, a ring-like structure, which allows the parasite to penetrate the host cell, folding the host's plasma membrane around itself for disguise in the hosts' cytoplasm. Some of the constituents of the moving junction have been identified in recent years and researchers have started to elucidate their roles during invasion. In a recent study published in Science, a French/Canadian team of researchers led by Maryse Lebrun and Martin Boulanger provide detailed insight into the core structure of the moving junction and explain how it can resist the strong forces that occur during invasion.

After the parasite has become attached to its host cell with the help of adhesion molecules that recognize carbohydrates on the host's surface, it injects a set of proteins that initiate intrusion by establishing an intimate contact zone between the plasma membranes of the host and parasite. For this purpose, the parasite produces receptor proteins and the appropriate ligands, which are secreted by specialized organelles called micronemes and rhoptries, respectively. The rhoptry proteins are injected into the host cell's cytoplasm where they form the rhoptry neck (RON) complex, which is anchored to the hosts' plasma membrane by RON2, a transmembrane protein whose extracellular part functions as a ligand for parasite docking. The micronemes secrete apical membrane antigen 1 (AMA1), which is the receptor for RON2, on the surface of the parasite. The assembled AMA1–RON complexes are an essential part of the moving junction ring, which is finally pulled backwards during intrusion driven by the parasite's actin–myosin motor.

To examine the precise nature of the AMA1–RON2 interaction in the Toxoplasma gondii parasite, the scientists mapped and characterized the AMA1 binding site of RON2. They were successful in narrowing down the binding site of RON2 to a region of 37 amino acids, which is stabilized by a disulphide bridge between two cysteines and forms a U-shaped loop. Next, they crystallized the AMA1 receptor in complex with a synthetic version of the U-shaped RON2 peptide to reveal fascinating details of the binding site. Most strikingly, they found that the loop of the RON2 peptide functions like a grappling hook. It is inserted deeply into a hydrophobic groove on the surface of AMA1, allowing the junction to withstand the strong mechanical forces that occur while pulling back the moving junction ring. Comparing this structure with another one obtained previously for the AMA1 receptor without the ligand suggests that major conformational changes occur upon RON2 binding, which optimize shape and charge complementarity between AMA1 and the RON2 peptide for a perfect fit.

Thanks to the laborious work of Lebrun, Boulanger and their colleagues, we now have deep structural insight into the moving junction's core structure, much of which can be applied to help us understand the function of the moving junction in the malaria parasite as it is highly conserved in Apicomplexian protozoans. Knowing the parasites' trick with the grappling hook may turn out to be extremely helpful for developing therapeutic antibodies, peptides and drugs that block the binding site and hence prevent parasite invasion.

• © 2011.