Abstract
Host cell traversal by Plasmodium, the protozoan cause of malaria, is an essential part of this parasite's virulence. In this process, the parasite enters a host cell through a parasite-induced pore, traverses the host cell, and then exits the host cell. Two P. berghei proteins, SPECT1 and SPECT2, are required for host cell traversal by the sporozoite form of the parasite. In the absence of either, no pore formation is observed. While SPECT2 has sequence homology to pore-forming proteins, SPECT1 has no homology to proteins of known structure or function. Here we present the 2.75 Å resolution structure of a slightly truncated version of P. berghei SPECT1. The structure reveals that the protein forms a four-helix bundle, with the rare feature of having all of these helices in parallel or antiparallel alignment. Also notable is the presence of a large, conserved, hydrophobic internal cavity in the protein, which may constitute a ligand-binding site or be indicative of partial instability in SPECT1, or both. The structure of SPECT1 will make possible targeted mutagenesis experiments aimed at understanding its mechanism of action in host cell traversal.
Highlights
Malaria exerts a global burden on human health and welfare, being endemic in 100 countries and causing 250 million clinical illnesses and 1 million deaths each year [1, 2]
We found that PbSPECT1 forms a four-helix bundle, with the rare feature of having all of these helices in parallel or antiparallel alignment
PbSPECT1D24 was expressed in E. coli, purified, and crystallized
Summary
Malaria exerts a global burden on human health and welfare, being endemic in 100 countries and causing 250 million clinical illnesses and 1 million deaths each year [1, 2]. This devastating disease is caused by the infective sporozoite form of the protozoan parasite Plasmodium, which is introduced into the dermis of a host through the bite of an infected female Anopheline mosquito. Sporozoites are highly motile and transit from the dermis through the circulatory system to the liver, where they invade hepatocytes and mature into the red blood cell-infective form of the parasite [3, 4]. There appears to be no cell type specificity for host cell traversal, suggesting that only Plasmodium factors are important for this process
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