Structural highlights
Publication Abstract from PubMedMalaria parasite UIS3 (Upregulated in Infective Sporozoites gene 3) is essential for sporozoite development in infected hepatocytes. UIS3 encodes for a membrane protein which is localized to the parasite parasitophorous vacuolar membrane in infected hepatocytes. We describe here 2.5A resolution crystal structure of Plasmodium falciparum UIS3 soluble domain (PfUIS(3130-229)) in complex with the lipid phosphatidylethanolamine (PE). PfUIS(3130-229) is a novel, compact and all alpha helical structure bound to one molecule of phosphatidylethanolamine (PE). The PfUIS(3130-229)-PE complex structure reveals a novel binding site with specific interactions between PfUIS(3130-229)and the PE head group. One acyl chain of PE wraps around part of PfUIS(3130-229)and docks onto a hydrophobic channel. We additionally provide new structural and biochemical evidence of PfUIS(3130-229)interactions with lipids (phosphatidylethanolamine), with phospholipid liposomes and with the human liver fatty acid binding protein (LFABP). The direct interaction of PfUIS(3130-229)with LFABP most likely provides the parasite with a conduit for importing essential fatty acids/lipids. Therefore, our analyses have implications for lipid transport into the parasite during the rapid growth phases of sporozoites. Given that PfUIS3 is essential for establishment of liver stage infection by P. falciparum, our data provide a new target for abrogating parasite development within liver cells before typical symptoms of malaria can manifest. Crystal structure of soluble domain of malaria sporozoite protein UIS3 in complex with lipid.,Sharma A, Yogavel M, Akhouri RR, Gill J, Sharma A J Biol Chem. 2008 Jun 23;. PMID:18577521[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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