Var2CSA minimal CSA binding region is located within the N-terminal region.

Var2CSA, a key molecule linked with pregnancy-associated malaria (PAM), causes sequestration of Plasmodium falciparum infected erythrocytes (PEs) in the placenta by adhesion to chondroitin sulfate A (CSA). Var2CSA possesses a 300 kDa extracellular region composed of six Duffy-binding like (DBL) doma...

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Autores principales:	Anand Srivastava, Stéphane Gangnard, Sébastien Dechavanne, Farroudja Amirat, Anita Lewit Bentley, Graham A Bentley, Benoît Gamain
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/66c2e98ae51745d387e6c420e2cdcbfb
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spelling	oai:doaj.org-article:66c2e98ae51745d387e6c420e2cdcbfb2021-11-18T06:53:40ZVar2CSA minimal CSA binding region is located within the N-terminal region.1932-620310.1371/journal.pone.0020270https://doaj.org/article/66c2e98ae51745d387e6c420e2cdcbfb2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625526/?tool=EBIhttps://doaj.org/toc/1932-6203Var2CSA, a key molecule linked with pregnancy-associated malaria (PAM), causes sequestration of Plasmodium falciparum infected erythrocytes (PEs) in the placenta by adhesion to chondroitin sulfate A (CSA). Var2CSA possesses a 300 kDa extracellular region composed of six Duffy-binding like (DBL) domains and a cysteine-rich interdomain region (CIDRpam) module. Although initial studies implicated several individual var2CSA DBL domains as important for adhesion of PEs to CSA, new studies revealed that these individual domains lack both the affinity and specificity displayed by the full-length extracellular region. Indeed, recent evidence suggests the presence of a single CSA-binding site formed by a higher-order domain organization rather than several independent binding sites located on the different domains. Here, we search for the minimal binding region within var2CSA that maintains high affinity and specificity for CSA binding, a characteristic feature of the full-length extracellular region. Accordingly, truncated recombinant var2CSA proteins comprising different domain combinations were expressed and their binding characteristics assessed against different sulfated glycosaminoglycans (GAGs). Our results indicate that the smallest region within var2CSA with similar binding properties to those of the full-length var2CSA is DBL1X-3X. We also demonstrate that inhibitory antibodies raised in rabbit against the full-length DBL1X-6ε target principally DBL3X and, to a lesser extent, DBL5ε. Taken together, our results indicate that efforts should focus on the DBL1X-3X region for developing vaccine and therapeutic strategies aimed at combating PAM.Anand SrivastavaStéphane GangnardSébastien DechavanneFarroudja AmiratAnita Lewit BentleyGraham A BentleyBenoît GamainPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20270 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anand Srivastava Stéphane Gangnard Sébastien Dechavanne Farroudja Amirat Anita Lewit Bentley Graham A Bentley Benoît Gamain Var2CSA minimal CSA binding region is located within the N-terminal region.
description	Var2CSA, a key molecule linked with pregnancy-associated malaria (PAM), causes sequestration of Plasmodium falciparum infected erythrocytes (PEs) in the placenta by adhesion to chondroitin sulfate A (CSA). Var2CSA possesses a 300 kDa extracellular region composed of six Duffy-binding like (DBL) domains and a cysteine-rich interdomain region (CIDRpam) module. Although initial studies implicated several individual var2CSA DBL domains as important for adhesion of PEs to CSA, new studies revealed that these individual domains lack both the affinity and specificity displayed by the full-length extracellular region. Indeed, recent evidence suggests the presence of a single CSA-binding site formed by a higher-order domain organization rather than several independent binding sites located on the different domains. Here, we search for the minimal binding region within var2CSA that maintains high affinity and specificity for CSA binding, a characteristic feature of the full-length extracellular region. Accordingly, truncated recombinant var2CSA proteins comprising different domain combinations were expressed and their binding characteristics assessed against different sulfated glycosaminoglycans (GAGs). Our results indicate that the smallest region within var2CSA with similar binding properties to those of the full-length var2CSA is DBL1X-3X. We also demonstrate that inhibitory antibodies raised in rabbit against the full-length DBL1X-6ε target principally DBL3X and, to a lesser extent, DBL5ε. Taken together, our results indicate that efforts should focus on the DBL1X-3X region for developing vaccine and therapeutic strategies aimed at combating PAM.
format	article
author	Anand Srivastava Stéphane Gangnard Sébastien Dechavanne Farroudja Amirat Anita Lewit Bentley Graham A Bentley Benoît Gamain
author_facet	Anand Srivastava Stéphane Gangnard Sébastien Dechavanne Farroudja Amirat Anita Lewit Bentley Graham A Bentley Benoît Gamain
author_sort	Anand Srivastava
title	Var2CSA minimal CSA binding region is located within the N-terminal region.
title_short	Var2CSA minimal CSA binding region is located within the N-terminal region.
title_full	Var2CSA minimal CSA binding region is located within the N-terminal region.
title_fullStr	Var2CSA minimal CSA binding region is located within the N-terminal region.
title_full_unstemmed	Var2CSA minimal CSA binding region is located within the N-terminal region.
title_sort	var2csa minimal csa binding region is located within the n-terminal region.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/66c2e98ae51745d387e6c420e2cdcbfb
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Var2CSA minimal CSA binding region is located within the N-terminal region.

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