Release of Plasmodium sporozoites requires proteins with histone-fold dimerization domains.

Tomasino Pace,Giulia Peruzzi,Vassiliki Varamogianni-Mamatsi,Inga Siden-Kiamos,Chiara Currà,Célia R S Garcia,Marta Ponzi,Roberta Spaccapelo,Renate Gessmann,Lefteris Spanos,Leonardo Picci

doi:10.1038/ncomms13846

Abstract

The sporozoite, the stage of the malaria parasite transmitted by the mosquito, first develops for ∼2 weeks in an oocyst. Rupture of the oocyst capsule is required for release of sporozoites, which then transfer to the salivary gland where they are injected into a new host. Here we identify two parasite proteins that we call oocyst rupture proteins 1 (ORP1) and ORP2. These proteins have a histone-fold domain (HFD) that promotes heterodimer formation in the oocyst capsule at the time of rupture. Oocyst rupture is prevented in mutants lacking either protein. Mutational analysis confirms the HFD as essential for ORP1 and ORP2 function, and heterodimer formation was verified in vitro. These two proteins are potential targets for blocking transmission of the parasite in the mosquito.

Highlights

The sporozoite, the stage of the malaria parasite transmitted by the mosquito, first develops for B2 weeks in an oocyst
oocyst rupture proteins 1 (ORP1) is located in the oocyst capsule, whereas ORP2 is re-localized from the oocyst cytoplasm to the capsule at the time when mature sporozoites have formed
The orp[2] gene product (PBANKA_1303400, 875 amino acids) has an amino-terminal histone-fold domain (HFD), which is most similar to NF-YC of plants and animals, and HAP5 of yeast (Fig. 1a,c)

Summary

Introduction

The sporozoite, the stage of the malaria parasite transmitted by the mosquito, first develops for B2 weeks in an oocyst. We identify two parasite proteins that we call oocyst rupture proteins 1 (ORP1) and ORP2 These proteins have a histone-fold domain (HFD) that promotes heterodimer formation in the oocyst capsule at the time of rupture. Mutational analysis confirms the HFD as essential for ORP1 and ORP2 function, and heterodimer formation was verified in vitro These two proteins are potential targets for blocking transmission of the parasite in the mosquito. ORP1 is located in the oocyst capsule, whereas ORP2 is re-localized from the oocyst cytoplasm to the capsule at the time when mature sporozoites have formed Taken together, these findings allows us to hypothesize that interaction of the two ORP proteins in the capsule, directly or indirectly, leads to a destabilization of this structure allowing the sporozoites to escape into the mosquito haemocoel

Methods

Results

Conclusion