Can any lessons be learned from the ambiguous glycan binding of PfEMP1 domains?
Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) accumulating in the placenta and has dire consequences for both mother and child. The multi-domain antigen VAR2CSA confers specific adhesion of IEs to chondroitin sulphate A (CSA) in the placenta, and is the leading PAM vaccine candidate. Recent data from different laboratories show that the binding properties of individual VAR2CSA domains do not reflect the native CSA-specific adhesion of IEs, which questions the relevance of the information obtained from single domain binding assays and co-crystallization experiments. Here, we discuss the implications of these findings for VAR2CSA vaccine development and highlight the need for studying the native structure of this protein.
Dahlbäck
Madeleine
M
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), CSS, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark. dahlback@sund.ku.dk <dahlback@sund.ku.dk>
Nielsen
Morten A
MA
Salanti
Ali
A
D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002809:Chondroitin Sulfates / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D006801:Humans; D017780:Malaria Vaccines; D010963:Plasmodium falciparum / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D011134:Polysaccharides; D015800:Protozoan Proteins; C512601:VAR2CSA protein, Plasmodium falciparum; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002809:Chondroitin Sulfates