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

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 t...

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Autores principales:	Pernille Andersen, Morten A Nielsen, Mafalda Resende, Thomas S Rask, Madeleine Dahlbäck, Thor Theander, Ole Lund, Ali Salanti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cdfa653f3eb149debda6a0fa2fc76a28
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spelling	oai:doaj.org-article:cdfa653f3eb149debda6a0fa2fc76a282021-11-25T05:46:43ZStructural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.1553-73661553-737410.1371/journal.ppat.0040042https://doaj.org/article/cdfa653f3eb149debda6a0fa2fc76a282008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18282103/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pregnancy-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.Pernille AndersenMorten A NielsenMafalda ResendeThomas S RaskMadeleine DahlbäckThor TheanderOle LundAli SalantiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 2, p e42 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Pernille Andersen Morten A Nielsen Mafalda Resende Thomas S Rask Madeleine Dahlbäck Thor Theander Ole Lund Ali Salanti Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
description	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.
format	article
author	Pernille Andersen Morten A Nielsen Mafalda Resende Thomas S Rask Madeleine Dahlbäck Thor Theander Ole Lund Ali Salanti
author_facet	Pernille Andersen Morten A Nielsen Mafalda Resende Thomas S Rask Madeleine Dahlbäck Thor Theander Ole Lund Ali Salanti
author_sort	Pernille Andersen
title	Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
title_short	Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
title_full	Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
title_fullStr	Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
title_full_unstemmed	Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.
title_sort	structural insight into epitopes in the pregnancy-associated malaria protein var2csa.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/cdfa653f3eb149debda6a0fa2fc76a28
work_keys_str_mv	AT pernilleandersen structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT mortenanielsen structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT mafaldaresende structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT thomassrask structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT madeleinedahlback structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT thortheander structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT olelund structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa AT alisalanti structuralinsightintoepitopesinthepregnancyassociatedmalariaproteinvar2csa
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Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA.

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