Adaptations in Plasmodium tubulin determine unique microtubule architectures, mechanics and drug susceptibility

Abstract

Microtubules are ubiquitous yet diverse cytoskeleton filaments. However, tubulin conservation presents challenges in understanding the origins of diverse microtubule architectures. The mechanisms by which microtubule architecture varies through the life cycle of the malaria-causing parasite Plasmodium are not understood and provide a valuable framework for exploring how intrinsic properties of tubulin contribute to architectural variety. Using parasite-purified tubulin, we determined structures of P. falciparum microtubules by cryo-electron microscopy. Parasite-specific sequences change the tubulin dimer structure, thereby modifying drug susceptibility and polymer mechanical properties. Within the P. falciparum microtubule, lateral contacts are smaller but stronger, and the lattice is stiffer than in mammalian microtubules. Non-canonical microtubule architectures found in parasites are highly similar to those observed in vitro, validating the physiological relevance of these properties. Our findings show how evolutionary adaptation of tubulin modulates the material properties of the microtubule cytoskeleton.