Epitopes described in "Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA."

Article Authors:Pernille Andersen; Morten A Nielsen; Mafalda Resende; Thomas S Rask; Madeleine Dahlb├Ąck; Thor Theander; Ole Lund; Ali Salanti
Article Title:Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
Reference Detail
Reference ID:1012394
Abstract:Pregnancy-associated malaria is caused by Plasmodium falciparum malaria parasites binding specifically to chondroitin sulfate A in the placenta. This sequestration of parasites is a major cause of low birth weight in infants and anemia in the mothers. VAR2CSA, a polymorphic multi-domain protein of the PfEMP1 family, is the main parasite ligand for CSA binding, and identification of protective antibody epitopes is essential for VAR2CSA vaccine development. Attempts to determine the crystallographic structures of VAR2CSA or its domains have not been successful yet. In this study, we propose 3D models for each of the VAR2CSA DBL domains and we show that regions in the fold of VAR2CSA inter-domain 2 and a PfEMP1 CIDR domain seem to be homologous to the EBA-175 and Pk alpha-DBL fold. This suggests that ID2 could be a functional domain. We also identify regions of VAR2CSA present on the surface of native VAR2CSA by comparing reactivity of plasma containing anti-VAR2CSA antibodies in peptide array experiments before and after incubation with native VAR2CSA. By this method we identify conserved VAR2CSA regions targeted by antibodies that react with the native molecule expressed on infected erythrocytes. By mapping the data onto the DBL models we present evidence suggesting that the S1+S2 DBL sub-domains are generally surface-exposed in most domains, whereas the S3 sub-domains are less exposed in native VAR2CSA. These results comprise an important step towards understanding the structure of VAR2CSA on the surface of CSA-binding infected erythrocytes.
Affiliations:Center for Biological Sequence Analysis, BioCentrum-DTU, Denmark.
Reference Type:Literature
PubMed ID:18282103
Journal:PLoS Pathog
Journal Volume:4
Article Pages:e42
Journal ISSN:1553-7374
Article Chemical List:Antigens, Protozoan;Protozoan Proteins;Recombinant Proteins;VAR2CSA protein, Plasmodium falciparum;erythrocyte membrane protein 1, Plasmodium falciparum;Chondroitin Sulfates
Article MeSH List:Adult; Animals; Antigens, Protozoan(chemistry; immunology); Chondroitin Sulfates(metabolism); Epitope Mapping; Erythrocytes(immunology; metabolism; parasitology); Female; Genetic Variation; Humans; Malaria, Falciparum(blood; physiopathology); Male; Models, Molecular; Plasmodium falciparum(immunology); Pregnancy; Pregnancy Complications, Parasitic(blood); Protein Conformation; Protozoan Proteins(chemistry; immunology); Rabbits; Recombinant Proteins
Curation Last Updated:2015-06-05 01:21:07