Chimeras of P4-ATPase and Guanylate Cyclase in Pathogenic Protists

Apicomplexan parasites harbor chimeric proteins embodying P4-type ATPase and guanylate cyclase domains. Such proteins - serving as the actuator of cGMP signaling in this group of important pathogens - are indeed unusual in terms of their sheer size, modus operandi, and evolutionary repurposing. Much like the mythological Sphinx, a human-lion chimeric creature that posed challenging riddles, the P4-type ATPase-guanylate cyclase chimeras present both structural and functional conundrums. Here we review the function, topology, mechanism, and intramolecular coordination of the alveolate-specific chimeras in apicomplexan parasites. The steep technological challenge to understand these molecular Sphinxes will surely keep many interdisciplinary researchers busy in the next decades.