Leishmania: Fine mapping of the leishmanolysin molecule's conserved core domains involved in binding and internalization

Puentes, F, Guzman, F, Marin, V., Alonso, C., Patarroyo, M. E., and Moreno A, 1999. Leishmania: Fine mapping of the Leishmanolysin molecule's conserve d core domains involved in binding and internalization. Experimental Parasi tology 93, 7-22. The Leishmanolysin molecule's role in the uptake of Leishm ania parasites by the human U937 pro-myelocytic cell line was studied, usin g synthetic peptides representing the complete Leishmania (Viannia) guyanen sis Leishmanolysin protein aminoacid sequence. The particular peptides pres ent in two protein's core domains efficiently impaired the internalization of promastigotes from four different Leishmania species and modified the ki netics of the binding of heterologous recombinant Leishmanolysin protein. T he functional domains which exhibited this property represent a highly cons erved portion of the sequence among different Leishmania species. The pepti des' inhibitory activity correlated with their ability to bind molecules pr esent on the surface of the human cell line. One of the two functional core domains identified involves the previously described adhesive sequence (SR YD) and the putative zinc-binding motif (HExxH). The second functional core domain includes a third histidine residue coordinated with zinc which dete rmines the molecule's structural features. These findings indicate that the molecular interactions between Leishmanolysin's conserved domains and the macrophage surface molecules efficiently contribute to the parasite's inter nalization. Induction of neutralizing immune responses, which impair the ea rly parasite-host interaction described here, may be an important alternati ve in designing synthetic subunit human leishmaniasis vaccines. (C) 1999 Ac ademic Press.