Cationic charge and polyspecificity of an integrin domain regulates infectivity of malaria parasites

Cell-cell and cell-substrate adhesion is critical for many functions in life. In eukaryotes, I-domains mediate functions as divergent as tissue traversal by malaria-causing Plasmodium parasites as well as cell adhesion and migration by human leucocytes. The I-domain containing protein TRAP is important for Plasmodium sporozoite motility and invasion. Here we show that the I-domain of TRAP is required to mediate adhesional properties which can be partially preserved when the native I-domain is replaced by I-domains from human integrins or from an apicomplexan parasite that does not infect insects. By putting in vivo data and structural features in perspective we conclude that polyspecificity and positive charge around the ligand binding site of the I-domain are important for TRAP function. Our data suggest a highly preserved functionality of I-domains across eukaryotic evolution that is used by apicomplexan parasites to invade a broad range of tissues in a variety of hosts.