Polymorphisms in Erythrocyte Binding Antigens 140 and 181 Affect Function and Binding but Not Receptor Specificity in Plasmodium falciparum

Maier, AG; Baum, J; Smith, B; Conway, DJ; Cowman, AF

Author(s): Maier, AG; Baum, J; Smith, B; Conway, DJ; Cowman, AF;
Details: Publication Year 2009-04,Volume 77,Issue #4,Page 1689-1699
Journal Title: INFECTION AND IMMUNITY
Publication Type: Journal Article
Abstract: Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum utilizes multiple ligand-receptor interactions involving erythrocyte receptors and parasite erythrocyte binding proteins of the Duffy binding-like family. Erythrocyte binding antigen 175 (EBA-175) binds to glycophorin A, the most abundant protein on the human erythrocyte surface and EBA-140 (also known as BAEBL) binds to glycophorin C, while the receptor for EBA-181 (also known as JESEBL) remains unknown. EBA binding is mediated via region II, a highly structured extracellular domain that shows a degree of sequence variability between different laboratory strains/isolates. Here, we determined the influence of region II polymorphisms on host cell receptor binding and overall function during invasion of EBA-140, EBA-175, and EBA-181. Polymorphisms in the binding domains of EBA-140 and EBA-181 have been suggested previously to alter their respective receptor specificities. In our hands, these polymorphisms affected the levels of EBA-140 and EBA-181 binding to receptors but, critically, not the receptor specificities of these proteins. The degree of EBA-140 binding to glycophorin C correlates with the level of function for this ligand-receptor interaction in merozoite invasion. In contrast, EBA-175, which is highly polymorphic in region II, shows no variability in its ability to bind to its receptor, glycophorin A. Combined, these data highlight the importance of sequence variability in EBAs as driven by immune selection but not by receptor specificity.
Publisher: AMER SOC MICROBIOLOGY
Keywords: DIVERSIFYING SELECTION; INVASION PHENOTYPES; MEROZOITE INVASION; MALARIA PARASITES; STRUCTURAL BASIS; LIGAND EBA-175; HOST-CELL; PROTEIN; DOMAIN; VIVAX
Publisher's Version: https://doi.org/10.1128/IAI.01331-08
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-04-01 12:00:00