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

TL;DR

The study reveals how adaptations in Plasmodium tubulin lead to unique microtubule structures and drug responses.

Contribution

The work identifies parasite-specific tubulin adaptations that alter microtubule architecture and drug susceptibility.

Findings

Parasite-specific tubulin sequences modify dimer structure and drug susceptibility.

P. falciparum microtubules have stronger lateral contacts and a stiffer lattice compared to brain microtubules.

Non-canonical microtubule architectures in parasites are similar to those observed in vitro.

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 determine P. falciparum microtubule structures by cryo-electron microscopy. Parasite-specific sequences change the tubulin dimer structure, suggesting how drug susceptibility and polymer properties are modified. Within the P. falciparum microtubule, lateral contacts are smaller but stronger, and the lattice is stiffer than in brain 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.

Tubulin conservation presents a challenge to understanding microtubules’ diverse functions in eukaryotes. Here, the authors characterize the structures of P. falciparum microtubules to show how evolutionary adaptation of tubulin modulates the material properties of the cytoskeleton.

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