MSP119 miniproteins can serve as targets for invasion inhibitory antibodies in plasmodium falciparum provided they contain the correct domains for cell surface trafficking.

Gilson, Paul R., O'Donnell, Rebecca A., Nebl, Thomas, Sanders, Paul R., Wickham, Mark E., McElwain, Terry F., de Koning-Ward, Tania F. and Crabb, Brendan S. 2008, MSP119 miniproteins can serve as targets for invasion inhibitory antibodies in plasmodium falciparum provided they contain the correct domains for cell surface trafficking., Molecular microbiology, vol. 68, no. 1, pp. 124-138.

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Title MSP119 miniproteins can serve as targets for invasion inhibitory antibodies in plasmodium falciparum provided they contain the correct domains for cell surface trafficking.
Author(s) Gilson, Paul R.
O'Donnell, Rebecca A.
Nebl, Thomas
Sanders, Paul R.
Wickham, Mark E.
McElwain, Terry F.
de Koning-Ward, Tania F.
Crabb, Brendan S.
Journal name Molecular microbiology
Volume number 68
Issue number 1
Start page 124
End page 138
Total pages 15
Publisher Wiley-Blackwell
Place of publication Oxford, England
Publication date 2008-04
ISSN 0950-382X
1365-2958
Keyword(s) antibodies
protozoan immunology
antigens
protozoan immunology
merozoite surface protein 1 metabolism
plasmodium falciparum metabolism
Summary Antibodies from malaria-exposed individuals can agglutinate merozoites released from Plasmodium schizonts, thereby preventing them from invading new erythrocytes. Merozoite coat proteins attached to the plasma membrane are major targets for host antibodies and are therefore considered important malaria vaccine candidates. Prominent among these is the abundant glycosylphosphatidylinositol (GPI)-anchored merozoite surface protein 1 (MSP1) and particularly its C-terminal fragment (MSP1(19)) comprised of two epidermal growth factor (EGF)-like modules. In this paper, we revisit the role of agglutination and immunity using transgenic fluorescent marker proteins. We describe expression of heterologous MSP1(19)'miniproteins' on the surface of Plasmodium falciparum merozoites. To correctly express these proteins, we determined that GPI-anchoring and the presence of a signal sequence do not allow default export of proteins from the endoplasmic reticulum to merozoite surface and that extra sequence elements are required. The EGFs are insufficient for correct trafficking unless they are fused to additional residues that normally reside upstream of this fragment. Antibodies specifically targeting the surface-expressed miniprotein can inhibit erythrocyte invasion in vitro despite the presence of endogenous MSP1. Using a line expressing a green fluorescent protein-MSP1 fusion protein, we demonstrate that one mode of inhibition by antibodies targeting the MSP1(19) domain is the rapid agglutinating of merozoites prior to erythrocyte attachment.
Language eng
Field of Research 110803 Medical Parasitology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, Wiley-Blackwell Publishing
Persistent URL http://hdl.handle.net/10536/DRO/DU:30028161

Document type: Journal Article
Collection: School of Medicine
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