4.7 Article

Conformational change of Plasmodium TRAP is essential for sporozoite migration and transmission

Journal

EMBO REPORTS
Volume 24, Issue 7, Pages -

Publisher

WILEY
DOI: 10.15252/embr.202357064

Keywords

adhesin; cell migration; gliding motility; integrins; malaria

Ask authors/readers for more resources

Eukaryotic cell adhesion and migration rely on surface adhesins connecting extracellular ligands to the intracellular actin cytoskeleton. Plasmodium sporozoites utilize adhesion and gliding motility for transmission and colonization purposes. The role of the TRAP adhesin and the importance of its conformational states in sporozoite behavior were studied, revealing that dynamic conformational change is required for ligand binding, gliding motility, and organ invasion, thus impacting sporozoite transmission.
Eukaryotic cell adhesion and migration rely on surface adhesins connecting extracellular ligands to the intracellular actin cytoskeleton. Plasmodium sporozoites are transmitted by mosquitoes and rely on adhesion and gliding motility to colonize the salivary glands and to reach the liver after transmission. During gliding, the essential sporozoite adhesin TRAP engages actin filaments in the cytoplasm of the parasite, while binding ligands on the substrate through its inserted (I) domain. Crystal structures of TRAP from different Plasmodium species reveal the I domain in closed and open conformations. Here, we probe the importance of these two conformational states by generating parasites expressing versions of TRAP with the I domain stabilized in either the open or closed state with disulfide bonds. Strikingly, both mutations impact sporozoite gliding, mosquito salivary gland entry, and transmission. Absence of gliding in sporozoites expressing the open TRAP I domain can be partially rescued by adding a reducing agent. This suggests that dynamic conformational change is required for ligand binding, gliding motility, and organ invasion and hence sporozoite transmission from mosquito to mammal.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available