Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors.
In: Molecular Microbiology, Jg. 67 (2008), Heft 1, S. 78-87
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Zugriff:
The Duffy binding-like (DBL) domain is a key adhesive module in Plasmodium falciparum, present in both erythrocyte invasion ligands (EBLs) and the large and diverse P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of cytoadherence receptors. DBL domains bind a variety of different host receptors, including intercellular adhesion molecule 1 (ICAM-1), a receptor interaction that may have a role in infected erythrocyte binding to cerebral blood vessels and cerebral malaria. In this study, we expressed the nearly full complement of DBLβ-C2 domains from the IT4/25/5 (IT4) parasite isolate and showed that ICAM-1-binding domains (DBLβ-C2ICAM-1) were confined to group B and group C PfEMP1 proteins and were not present in group A, suggesting that ICAM-1 selection pressure differs between PfEMP1 groups. To further dissect the molecular determinants of binding, we modelled a DBLβ-C2ICAM-1 domain on a solved DBL structure and created alanine substitution mutants in two DBLβ-C2ICAM-1 domains. This analysis indicates that the DBLβ-C2::ICAM-1 interaction maps to the equivalent glycan binding region of EBLs, and suggests a general model for how DBL domains evolve under dual selection for host receptor binding and immune evasion. [ABSTRACT FROM AUTHOR]
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Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors.
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Autor/in / Beteiligte Person: | Howell, Dasein P. G. ; Levin, Emily A. ; Springer, Amy L. ; Kraemer, Susan M. ; Phippard, David J. ; Schief, William R. ; Smith, Joseph D. |
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Zeitschrift: | Molecular Microbiology, Jg. 67 (2008), Heft 1, S. 78-87 |
Veröffentlichung: | 2008 |
Medientyp: | academicJournal |
ISSN: | 0950-382X (print) |
DOI: | 10.1111/j.1365-2958.2007.06019.x |
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