Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is...
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doaj-4d93b7dffb8048b6804bbe02d5ef6b4c2021-10-01T04:52:20ZengElsevierInternational Journal of Infectious Diseases1201-97122021-11-011123539Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccineJasmita Gill0Soumyananda Chakraborti1Praveen Bharti2Amit Sharma3ICMR-National Institute of Malaria Research, New Delhi, India; Correspondence:ICMR-National Institute of Malaria Research, New Delhi, IndiaICMR-National Institute of Malaria Research, New Delhi, IndiaICMR-National Institute of Malaria Research, New Delhi, India; Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaPlacental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria.http://www.sciencedirect.com/science/article/pii/S1201971221006871Placental malariaVAR2CSAPlacental malaria vaccineField isolates, Structural mapping |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma |
spellingShingle |
Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine International Journal of Infectious Diseases Placental malaria VAR2CSA Placental malaria vaccine Field isolates, Structural mapping |
author_facet |
Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma |
author_sort |
Jasmita Gill |
title |
Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine |
title_short |
Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine |
title_full |
Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine |
title_fullStr |
Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine |
title_full_unstemmed |
Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine |
title_sort |
structural insights into global mutations in the ligand-binding domain of var2csa and its implications on placental malaria vaccine |
publisher |
Elsevier |
series |
International Journal of Infectious Diseases |
issn |
1201-9712 |
publishDate |
2021-11-01 |
description |
Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria. |
topic |
Placental malaria VAR2CSA Placental malaria vaccine Field isolates, Structural mapping |
url |
http://www.sciencedirect.com/science/article/pii/S1201971221006871 |
work_keys_str_mv |
AT jasmitagill structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT soumyanandachakraborti structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT praveenbharti structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT amitsharma structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine |
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