Plasmodium yoelii:The Role of the Individual Epidermal Growth Factor-like Domains of the Merozoite Surface Protein-1 in Protection from Malaria

1996 ◽  
Vol 82 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Paul A. Calvo ◽  
Thomas M. Daly ◽  
Carole A. Long
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1 ◽  
Epidermal Growth ◽  
The Individual

scholarly journals A Common Cross-species Function for the Double Epidermal Growth Factor-like Modules of the Highly DivergentPlasmodiumSurface Proteins MSP-1 and MSP-8

2004 ◽  
Vol 279 (19) ◽  
pp. 20147-20153 ◽  
Author(s):  
Damien R. Drew ◽  
Rebecca A. O'Donnell ◽  
Brian J. Smith ◽  
Brendan S. Crabb
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Drug Targets ◽  
Point Mutations ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Parasite Line ◽  
Asexual Blood Stage ◽  
Epidermal Growth

An understanding of structural and functional constraints on the C-terminal double epidermal growth factor (EGF)-like modules of merozoite surface protein (MSP)-1 and related proteins is of importance to the development of these molecules as malaria vaccines and drug targets. Using allelic replacement, we show thatPlasmodium falciparumparasites can invade erythrocytes and grow efficiently in the absence of an MSP-1 protein with authentic MSP-1 EGF domains. In this mutant parasite line, the MSP-1 EGFs were replaced by the corresponding double EGF module fromP. bergheiMSP-8, the sequence of which shares only low identity with its MSP-1 counterpart. Hence, the C-terminal EGF domains of at least somePlasmodiumsurface proteins appear to perform the same function in asexual blood-stage development. Mapping the surface location of the few residues that are common to these functionally complementary EGF modules revealed the presence of a highly conserved pocket of potential functional significance. In contrast to MSP-8, an even more divergent double EGF module, that from the sexual stage protein PbS25, was not capable of complementing MSP-1 EGF function. More surprisingly, two chimeric double EGF modules comprising hybrids of the EGF domains fromP. falciparumandP. chabaudiMSP-1 were also not capable of replacing theP. falciparumMSP-1 EGF module. Together, these data suggest that although the MSP-1 EGFs can accommodate extensive sequence diversity, there appear to be constraints that may restrict the simple accumulation of point mutations in the face of immune pressure in the field.

scholarly journals A Protective Glycosylphosphatidylinositol-Anchored Membrane Protein of Plasmodium yoelii Trophozoites and Merozoites Contains Two Epidermal Growth Factor-Like Domains

2000 ◽  
Vol 68 (11) ◽  
pp. 6189-6195 ◽  
Author(s):  
James M. Burns ◽  
Carla C. Belk ◽  
Patricia D. Dunn
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
High Titer ◽  
Rabbit Antiserum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Surface Proteins ◽  
Reading Frame ◽  
Epidermal Growth

ABSTRACT Using sera from mice immunized and protected againstPlasmodium yoelii malaria, we identified a novel blood-stage antigen gene, pypag-2. The 2.1-kbpypag-2 cDNA contains a single open reading frame that encodes a 409-amino-acid protein with a predicted molecular mass of 46.8 kDa. Unlike many characterized plasmodial antigens, blocks of tandemly repeated amino acids are lacking in the pypAg-2 protein sequence. Recombinant pypAg-2, comprising the full-length protein minus the predicted N-terminal signal and C-terminal anchor sequences, was produced and used to raise a high-titer polyclonal rabbit antiserum. This antiserum was used to identify and characterize the native protein through immunoblotting, immunoprecipitation and immunofluorescence assays. Consistent with the presence of a glycosylphosphatidylinositol anchor, pypAg-2 fractionated with the detergent phase of Triton X-114-solubilized proteins and could be metabolically labeled with [3H]palmitic acid. By immunofluorescence, pypAg-2 expression was localized to both the trophozoite and merozoite membranes. Similar to Plasmodium falciparum merozoite surface protein 1, pypAg-2 contains two C-terminal epidermal growth factor (EGF)-like domains. Most importantly, immunization with recombinant pypAg-2 protected mice against lethal P. yoeliimalaria. Thus, pypAg-2 is a target of protective immune responses and represents a novel addition to the family of merozoite surface proteins that contain one or more EGF-like domains.

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