Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum

Tolia, N. H., Enemark, E. J., Sim, B. K., Joshua-Tor, L. (2005) Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Cell, 122 (2). pp. 183-93. ISSN 0092-8674 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/16051144
DOI: 10.1016/j.cell.2005.05.033

Abstract

Erythrocyte binding antigen 175 (EBA-175) is a P. falciparum protein that binds the major glycoprotein found on human erythrocytes, glycophorin A, during invasion. Here we present the crystal structure of the erythrocyte binding domain of EBA-175, RII, which has been established as a vaccine candidate. Binding sites for the heavily sialylated receptor glycophorin A are proposed based on a complex of RII with a glycan that contains the essential components required for binding. The dimeric organization of RII displays two prominent channels that contain four of the six observed glycan binding sites. Each monomer consists of two Duffy binding-like (DBL) domains (F1 and F2). F2 more prominently lines the channels and makes the majority of the glycan contacts, underscoring its role in cytoadherence and in antigenic variation in malaria. Our studies provide insight into the mechanism of erythrocyte invasion by the malaria parasite and aid in rational drug design and vaccines.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Antigens Protozoan chemistry metabolism Binding Sites COS Cells Cercopithecus aethiops Crystallography X-Ray Dimerization Erythrocyte Membrane metabolism parasitology Erythrocytes metabolism parasitology Glycophorin metabolism Humans Models Molecular Molecular Sequence Data Plasmodium falciparum physiology Polysaccharides chemistry metabolism Protein Structure Tertiary Protozoan Proteins chemistry metabolism Rosette Formation
Subjects: Investigative techniques and equipment > X-Ray Diffraction
Investigative techniques and equipment > x ray crystallography
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
Watson School > Publications
Depositing User: CSHL Librarian
Date Deposited: 05 Jan 2012 15:46
Last Modified: 05 Sep 2017 18:32
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URI: http://repository.cshl.edu/id/eprint/22722

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