Characterization of the DBL6e domain of the VAR2CSA protein involved in pregnancy-associated malaria: Nanobodies as tools for structural and functional studies
نویسنده
چکیده
Malaria is a devastating and complicated disease caused by the Plasmodium parasite. P. falciparum has developed a mechanism for evasion of immune responses and clearance from the blood stream by adhering to endothelial cells in different organs. This is achieved by the expression of P. falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the surface of infected red blood cells (iRBCs), which interact with specific receptors. Understanding the molecular mechanisms involved in this sequestration process is crucial in preventing severe malaria and the development of a blood-stage vaccine.
منابع مشابه
Llama immunization with full-length VAR2CSA generates cross-reactive and inhibitory single-domain antibodies against the DBL1X domain
VAR2CSA stands today as the leading vaccine candidate aiming to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of pregnancy associated malaria (PAM). The rational design of an efficient VAR2CSA-based vaccine relies on a profound understanding of the molecular interactions associated with P. falciparum infected erythrocyte sequestration in the ...
متن کاملProduction, crystallization and X-ray diffraction analysis of two nanobodies against the Duffy binding-like (DBL) domain DBL6∊-FCR3 of the Plasmodium falciparum VAR2CSA protein. Corrigendum
The VAR2CSA protein has been closely associated with pregnancy-associated malaria and is recognized as the main adhesin exposed on the surface of Plasmodium falciparum-infected erythrocytes. Chondroitin sulfate A was identified as the main host receptor in the placenta. Single-domain heavy-chain camelid antibodies, more commonly called nanobodies, were selected and produced against the DBL6ℇ-FC...
متن کاملStructural 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 the PfEMP1 family, is the main parasite ligand for CSA binding, and identification of protective a...
متن کاملStructural insights into chondroitin sulfate binding in pregnancy-associated malaria.
Malaria during pregnancy is caused when parasite-infected erythrocytes accumulate within the placenta through interactions between the VAR2CSA protein on the infected erythrocyte surface and placental CSPGs (chondroitin sulfate proteoglycans). This interaction is the major target for therapeutics to treat or prevent pregnancy-associated malaria. Here we review the structural characterization of...
متن کاملEpitope Mapping and Topographic Analysis of VAR2CSA DBL3X Involved in P. falciparum Placental Sequestration
Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in malaria endemic areas. The syndrome is precipitated by accumulation of infected erythrocytes in placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts and a parasite-encoded protein on the surface of infected erythrocytes, believed to be VAR2CSA. VAR2CSA i...
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