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Duffy binding-like 1α adhesin from Plasmodium falciparum recognizes ABH histo-blood group saccharide in a type specific manner

Oliveira, Isadora A., Pol-Fachin, Laércio, de Carvalho, Sebastião T., Lins, Roberto D., Soares, Thereza A., Mohana-Borges, Ronaldo, Neves, Jorge L., Todeschini, Adriane R.
Carbohydrate polymers 2019 v.207 pp. 266-275
Plasmodium falciparum, adhesins, blood groups, cell adhesion, disease susceptibility, endothelial cells, epitopes, erythrocytes, malaria, nuclear magnetic resonance spectroscopy
The ability of erythrocytes, infected by Plasmodium falciparum, to adhere to endothelial cells (cytoadherence) and to capture uninfected erythrocyte (rosetting) is the leading cause of death by severe malaria. Evidences link the binding of the adhesin Duffy Binding Like1-α (DBL1α) domain to the ABH histo-blood antigens with formation of rosettes. Inspired by this very close relationship between the disease susceptibility and individual blood type, here we investigate the structural requirements involved in the interaction of DBL1α with A, B and H histo-blood determinants and their subtypes. Our results evidence the high preference of DBL1α to A epitopes, in comparison to B and H epitopes. DBL1α interacts with ABH epitopes in subtype specific manner, presenting a remarkable affinity for type 2 structures, Fucα1-2Galβ1-4GlcNAcβ1, particularly the A2 epitope. The contacts made by DBL1α binding pocket and the ABH histo-blood groups were mapped by theoretical methods and supported by NMR experiments.