期刊
PLOS ONE
卷 8, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0061323
关键词
-
资金
- National Institutes of Health [1R21AI064503, 1R56AI083668, 1R01AI092120]
- Foundation of the National Institutes of Health through the Grand Challenges in Global Health initiative [29202]
Plasmodium falciparum virulence has been ascribed to its ability to sequester in deep vascular beds, mediated by the variant surface antigen family PfEMP1 binding endothelial receptors like ICAM-1. We previously observed that naturally-acquired antibodies that block a PfEMP1 domain, DBL2 beta of PF11_0521 allele, from binding to the human ICAM1 receptor, reduce the risk of malaria hospitalization in children. Here, we find that DBL2 beta(PF11_0521) binds ICAM-1 in the low nM range and relate the structure of this domain with its function and immunogenicity. We demonstrate that the interaction with ICAM-1 is not impaired by point mutations in the N-terminal subdomain or in the flexible Loop 4 of DBL2 beta(PF11_0521), although both substructures were previously implicated in binding ICAM-1. These data will help to refine the existing model of DBL beta::ICAM-1 interactions. Antibodies raised against full-length DBL2 beta(PF11_0521), but not truncated forms lacking the N terminal fragment, block its interaction with ICAM-1. Our data suggest that full length domain is optimal for displaying functional epitopes and has a broad surface of interaction with ICAM-1 that is not disrupted by individual amino acid substitutions at putative key residues. This information might be important for the future design of anti-malarial vaccines based on PfEMP1 antigens.
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