![]() ![]() Therefore, understanding the molecular processes involved in male gamete development and flagella formation is of fundamental interest, and may offer new avenues for development of disease control 4. If male gamete motility is compromised, parasite transmission is blocked 3. In particular, the flagella-driven motility of male gametes, which develop from male gametocytes in the mosquito gut immediately on ingestion of a blood meal, is required to fertilise female gametes for onward progression of the life cycle. Given this diversity of functions, precise regulation of MT dynamics and organisation by cellular factors is absolutely essential for parasite survival. The microtubule (MT) cytoskeleton plays a number of important roles throughout this life cycle, including formation of the mitotic/meiotic spindles during the several replicative stages 1, during invasion of and egress from host cells and tissues 2, and in forming the motile flagella in male gametes 3. are intracellular parasites with a complex life cycle that alternates between mammalian hosts and mosquito vectors. Malaria-of which there were 241 million cases globally and 627,000 deaths in 2020 ( )-is caused by apicomplexan Plasmodium parasites. These data suggest that the mechanochemistry of Plasmodium kinesin-8Bs is functionally tuned to support flagella formation. ![]() ![]() Nevertheless, the neck linker region is required for motility and depolymerisation activities of these motors. berghei kinesin-8B exhibits a non-canonical structural response to ATP analogue binding such that neck linker docking is not induced. We determined these motors’ microtubule-bound structures using cryo-electron microscopy, which showed very similar modes of microtubule interaction in which Plasmodium-distinct sequences at the microtubule-kinesin interface influence motor function. Both motors drive ATP-dependent microtubule gliding, but also catalyse ATP-dependent microtubule depolymerisation. To understand the molecular basis of kinesin-8B’s essential role, we characterised the in vitro properties of kinesin-8B motor domains from P. The microtubule-based motor kinesin-8B is required for development of the flagellated Plasmodium male gamete, and its absence completely blocks parasite transmission. Plasmodium species cause malaria and kill hundreds of thousands annually.
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