Deciphering Membrane Protein Complexes in Plasmodium falciparum Gametocytes via Cross-Linking Mass Spectrometry and Structural Modeling

ABSTRACT: Malaria is a disease targeting the most vulnerable people. It is caused by the parasite Plasmodium falciparum, and is transmitted to humans by Anopheles mosquitos during a blood meal, who are in turn infected by the parasite if they feed on an infected human. While current eradication efforts focus on mosquito control, transmission blocking therapeutics will be critical for successful eradication. The parasite goes through several life stages and reproduces sexually. This reproduction is mediated by gametocytes, which are responsible for transmission from humans to mosquitos, and thus represent an excellent target for transmission blocking therapeutics. However, there is very little information on the composition and interactions of gametocyte-specific proteins, in particular membrane proteins. In order to fill this knowledge gap, we cultured the gametocytes and isolated their membrane fraction. We then used cross-linking mass-spectrometry as well as size-exclusion and strong-cation exchange fractionation to identify protein-protein interaction networks. The interactions identified encompass host-pathogen and pathogen-pathogen complexes, and are distributed among many cellular compartments. The results of this study extend the understanding of malaria gametocyte biology, and serve as a springboard to accelerate research into potentially transmission-blocking Malaria therapeutics.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Plasmodium Falciparum 58.1

TISSUE(S): Erythrocyte

SUBMITTER: Max Ruwolt  

LAB HEAD: Jan Kosinski

PROVIDER: PXD067699 | Pride | 2026-04-09

REPOSITORIES: Pride