Structure-function-immunogenicity studies of PfEMP1 domain DBL2βPF11_0521, a malaria parasite ligand for ICAM-1.
Structure-function-immunogenicity studies of PfEMP1 domain DBL2βPF11_0521, a malaria parasite ligand for ICAM-1.
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DOI：
10.1371/journal.pone.0061323
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Oleinikov AV
中科院分区：
文献类型：
--
作者：
Gullingsrud J;Saveria T;Amos E;Duffy PE;Oleinikov AV
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, DBL2β of PF11_0521 allele, from binding to the human ICAM1 receptor, reduce the risk of malaria hospitalization in children. Here, we find that DBL2βPF11_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 DBL2βPF11_0521, although both substructures were previously implicated in binding ICAM-1. These data will help to refine the existing model of DBLβ::ICAM-1 interactions. Antibodies raised against full-length DBL2βPF11_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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