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Crystal Structure of Soluble Domain of Malaria Sporozoite Protein UIS3 in Complex with Lipid*
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2008
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2008.
-
Abstract
- Malaria parasite UIS3 (up-regulated in infective sporozoites gene 3) is essential for sporozoite development in infected hepatocytes. UIS3 encodes for a membrane protein that is localized to the parasite parasitophorous vacuolar membrane in infected hepatocytes. We describe here 2.5-A resolution crystal structure of Plasmodium falciparum UIS3 soluble domain (PfUIS3(130-229)) in complex with the lipid phosphatidylethanolamine (PE). PfUIS3(130-229) is a novel, compact, and all alpha-helical structure bound to one molecule of PE. The PfUIS3(130-229)-PE complex structure reveals a novel binding site with specific interactions between PfUIS3(130-229) and the PE head group. One acyl chain of PE wraps around part of PfUIS3(130-229) and docks onto a hydrophobic channel. We additionally provide new structural and biochemical evidence of PfUIS3(130-229) interactions with lipids (phosphatidylethanolamine), with phospholipid liposomes, and with the human liver fatty acid-binding protein. The direct interaction of PfUIS3(130-229) with liver fatty acid-binding protein 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.
- Subjects :
- Plasmodium falciparum
Phospholipid
Protozoan Proteins
Crystallography, X-Ray
Fatty Acid-Binding Proteins
Biochemistry
Fatty acid-binding protein
Protein Structure, Secondary
03 medical and health sciences
chemistry.chemical_compound
Parasite hosting
Animals
Humans
Binding site
Molecular Biology
Lipid Transport
030304 developmental biology
Phosphatidylethanolamine
0303 health sciences
biology
030306 microbiology
Phosphatidylethanolamines
Membrane Proteins
Cell Biology
biology.organism_classification
3. Good health
Cell biology
Protein Structure, Tertiary
Membrane Transport, Structure, Function, and Biogenesis
chemistry
Membrane protein
Liver
Solubility
Hepatocytes
Hydrophobic and Hydrophilic Interactions
Subjects
Details
- Language :
- English
- ISSN :
- 1083351X and 00219258
- Volume :
- 283
- Issue :
- 35
- Database :
- OpenAIRE
- Journal :
- The Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....edaef059da68d68d5880465e2e7e3ced