1-s2.0-S0166685115300074-main.pdf (1.44 MB)
0/0

Identification of the minimal binding region of a Plasmodium falciparum IgM binding PfEMP1 domain

Download (1.44 MB)
journal contribution
posted on 18.02.2016 by Russell Wallis, J-P. Semblat, A. Ghumra, D. M. Czajkowsky, D. A. Mitchell, A. Raza, J. A. Rowe
Binding of host immunoglobulin is a common immune evasion mechanism demonstrated by microbial pathogens. Previous work showed that the malaria parasite Plasmodium falciparum binds the Fc-region of human IgM molecules, resulting in a coating of IgM on the surface of infected erythrocytes. IgM binding is a property of P. falciparum strains showing virulence-related phenotypes such as erythrocyte rosetting. The parasite ligands for IgM binding are members of the diverse P. falciparum Erythrocyte Membrane Protein One (PfEMP1) family. However, little is known about the amino acid sequence requirements for IgM binding. Here we studied an IgM binding domain from a rosette-mediating PfEMP1 variant, DBL4ζ of TM284var1, and found that the minimal IgM binding region mapped to the central region of the DBL domain, comprising all of subdomain 2 and adjoining parts of subdomains 1 and 3. Site-directed mutagenesis of charged amino acids within subdomain 2, predicted by molecular modelling to form the IgM binding site, showed no marked effect on IgM binding properties. Overall, this study identifies the minimal IgM binding region of a PfEMP1 domain, and indicates that the existing homology model of PfEMP1-IgM interaction is incorrect. Further work is needed to identify the specific interaction site for IgM within the minimal binding region of PfEMP1.
Logo branding

Categories

Keyword(s)

History

Citation

Molecular and Biochemical Parasitology, 2015, 201(1), pp. 76-82

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Molecular and Biochemical Parasitology

Publisher

Elsevier

issn

0166-6851

eissn

1872-9428

Acceptance date

08/06/2015

Copyright date

2015

Available date

18/02/2016

Publisher version

http://www.sciencedirect.com/science/article/pii/S0166685115300074

Language

en

Licence

Exports

Logo branding

Categories

Keyword(s)

Licence

Exports