Schistosoma mansoni: structural and biochemical characterization of two distinct Venus Kinase Receptors

Venus Kinase Receptors (VKRs) are atypical transmembrane proteins composed of an extracellular Venus FlyTrap module linked through a single helix to a tyrosine kinase domain similar to that of insulin receptors. This structure was first described in Schistosoma mansoni, then in a selected range of invertebrates, including many insects. The preferential expression of VKRs in larvae and gonads suggested their role in development and reproduction. While a single vkr gene was consistently found in all genomes, we identified two distinct vkr genes in S. mansoni. Our data indicated that Smvkr1 and Smvkr2 are very similar in structure and likely originated from gene duplication. Both genes are expressed in all the parasite stages and encode homologous proteins with a conserved VKR structure. Recombinant SmVKR1 and SmVKR2 exhibit tyrosine kinase activities dependent on the binding of distinct small ligand molecules. SmVKR1 and SmVKR2 could represent paralogs with different functions in the parasite.