Unknown

Dataset Information

0

Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.


ABSTRACT: Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.

SUBMITTER: Lennartz F 

PROVIDER: S-EPMC5374107 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications


Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1)  ...[more]

Similar Datasets

| S-EPMC5783720 | biostudies-literature
| S-EPMC7845591 | biostudies-literature
| S-EPMC4256257 | biostudies-literature
| S-EPMC3917906 | biostudies-literature
| S-EPMC3008175 | biostudies-literature
| S-EPMC4297295 | biostudies-literature
| S-EPMC4672576 | biostudies-literature
| S-EPMC3752466 | biostudies-literature
| S-EPMC3088720 | biostudies-literature
| S-EPMC5865037 | biostudies-literature