Human hemoglobin protects the parasite cytoskeleton during Plasmodium falciparum gametocyte development

ABSTRACT: Transmission of Plasmodium falciparum requires the differentiation of asexual parasites into male and female gametocytes, which undergo extensive cytoskeletal remodeling, assembling a non-canonical subpellicular microtubule (SPMT) network. Using single-particle cryo-electron microscopy, we determined structures of SPMTs isolated from developing gametocytes. Unexpectedly, we identified human hemoglobin as a prominent microtubule-associated factor that binds to P. falciparum SPMTs in a dimeric form rather than the canonical tetramer. Pharmacological perturbation of microtubules and hemoglobin isoform switching experiments demonstrate that this hemoglobin-SPMT association is essential for proper SPMT organization and gametocyte maturation. Together, these findings reveal a previously unrecognized strategy by which P. falciparum repurposes a host metabolic protein to stabilize its cytoskeleton, highlight the intimate co-evolution between parasite and host, and suggest new avenues to block malaria transmission.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Falciparum

TISSUE(S): Cell Culture

SUBMITTER: Sophe Alvarez  

LAB HEAD: Sophie Alvarez

PROVIDER: PXD082294 | Pride | 2026-10-15

REPOSITORIES: Pride