Abstract

The parasite that causes malaria invades and prospers in various tissues such as skin, blood, liver, gut, and salivary glands of its human and mosquito hosts. The invasion of many different kinds of cells implies that the parasite makes use of a diverse cell biology of receptor-ligand interactions. By determining the three-dimensional structures of receptor and ligand proteins, we are studying the interactions that allow the parasite to specifically target a particular type of cell to invade. The parasite receptors, being on the cell surface, are also prime candidates for the development of anti-malarial vaccines as immunity to malaria appears to correlate with immune responses to cell surface receptors. We have crystallized three malarial cell surface proteins and are working on several more. With x-ray diffraction data in hand for two receptors, we are proceeding to determine their three-dimensional structures. We have obtained x-ray data and are seeking improved crystals and data for two additional receptors. The receptors we are studying are candidates for inclusion in a vaccine and are expressed in several life stages of the malarial parasite. Through these studies we expect to reveal the overall shapes and the specific interactions of important receptors on the parasite.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000881-04
Application #
6986976
Study Section
(LIG)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Singh, Kavita; Gittis, Apostolos G; Nguyen, Phuc et al. (2008) Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A. Nat Struct Mol Biol 15:932-8
Singh, Kavita; Gittis, Apostolos G; Nguyen, Phuc et al. (2008) Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A. Nat Struct Mol Biol :
Klein, Michael M; Gittis, Apostolos G; Su, Hua-Poo et al. (2008) The cysteine-rich interdomain region from the highly variable plasmodium falciparum erythrocyte membrane protein-1 exhibits a conserved structure. PLoS Pathog 4:e1000147
Saxena, Ajay K; Wu, Yimin; Garboczi, David N (2007) Plasmodium p25 and p28 surface proteins: potential transmission-blocking vaccines. Eukaryot Cell 6:1260-5
Saxena, Ajay K; Singh, Kavita; Su, Hua-Poo et al. (2006) The essential mosquito-stage P25 and P28 proteins from Plasmodium form tile-like triangular prisms. Nat Struct Mol Biol 13:90-1
Burgess, Brandt R; Schuck, Peter; Garboczi, David N (2005) Dissection of merozoite surface protein 3, a representative of a family of Plasmodium falciparum surface proteins, reveals an oligomeric and highly elongated molecule. J Biol Chem 280:37236-45
Murphy, Patrick J M; Morishima, Yoshihiro; Kovacs, Jeffrey J et al. (2005) Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. J Biol Chem 280:33792-9
Saxena, Ajay K; Singh, Kavita; Long, Carole A et al. (2004) Preparation, crystallization and preliminary X-ray analysis of a complex between the Plasmodium vivax sexual stage 25 kDa protein Pvs25 and a malaria transmission-blocking antibody Fab fragment. Acta Crystallogr D Biol Crystallogr 60:2054-7
Saxena, Ajay K; Saul, Allan; Garboczi, David N (2004) Crystallization and preliminary X-ray analysis of the Plasmodium vivax sexual stage 25 kDa protein Pvs25, a transmission-blocking vaccine candidate for malaria. Acta Crystallogr D Biol Crystallogr 60:706-8
Garman, Scott C; Simcoke, William N; Stowers, Anthony W et al. (2003) Structure of the C-terminal domains of merozoite surface protein-1 from Plasmodium knowlesi reveals a novel histidine binding site. J Biol Chem 278:7264-9

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