The N-terminal amino acid sequences of the Plasmodium falciparum (FCB1) merozoite surface antigens of 42 and 36 kilodalton, both derived from the 185–195-kilodalton precursor

Heidrich, Hans-G.; Miettinen-Baumann, Arja; Eckerskorn, Christoph; Lottspeich, Friedrich

doi:10.1016/0166-6851(89)90006-6

Cited by 21 publications

(5 citation statements)

References 37 publications

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“…P. falciparum MSP1 is a polymorphic protein that exists in two major isoforms, typified by those of the 3D7 and FCB1 parasite isolates. N-terminal sequencing has mapped three positionally conserved primary processing sites in each of these MSP1 isoforms ( Blackman et al., 1991; Cooper and Bujard, 1992; Heidrich et al., 1989; Koussis et al., 2009; Stafford et al., 1994 ). The sites are referred to as 83/30, 30/38, and 38/42, after the approximate masses of the cleavage products ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Das

Hertrich

Perrin

et al. 2015

Cell Host & Microbe

159

184

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SummaryThe malaria parasite Plasmodium falciparum replicates within erythrocytes, producing progeny merozoites that are released from infected cells via a poorly understood process called egress. The most abundant merozoite surface protein, MSP1, is synthesized as a large precursor that undergoes proteolytic maturation by the parasite protease SUB1 just prior to egress. The function of MSP1 and its processing are unknown. Here we show that SUB1-mediated processing of MSP1 is important for parasite viability. Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress.

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Section: Resultsmentioning

confidence: 99%

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Das

Hertrich

Perrin

et al. 2015

Cell Host & Microbe

159

184

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“…, 1994; Koussis et al. , 2009) and others (Heidrich et al. , 1989) has precisely mapped all the primary processing sites in both the 3D7 and Wellcome types of MSP1.…”

Section: Resultsmentioning

confidence: 99%

“…A third relatively uncommon MSP1 form, initially identified in the RO-33 parasite isolate, entirely lacks block 2 (which is composed of variable Ser-Xaa-Xaa tripeptide repeats) but is otherwise similar to the 3D7 type (Certa et al, 1987;Peterson et al, 1988;Tanabe et al, 2007). Previous work by us (Blackman et al, 1991;Cooper and Bujard, 1992;Stafford et al, 1994;Koussis et al, 2009) and others (Heidrich et al, 1989) has precisely mapped all the primary processing sites in both the 3D7 and Wellcome types of MSP1. To examine the degree of amino acid conservation around these positions, sequences flanking the cleavage sites in all available full and partial P. falciparum MSP1 sequences deposited in PlasmoDB (http://plasmodb.org/ plasmo/) and GenBank (http://www.ncbi.nlm.nih.gov/) were examined by multiple alignment.…”

Section: Most Primary Processing Sites In Msp1 Are Dimorphicmentioning

confidence: 98%

Regulated maturation of malaria merozoite surface protein‐1 is essential for parasite growth

Child¹,

Epp

Bujard³

et al. 2010

Molecular Microbiology

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The malaria parasite Plasmodium falciparum invades erythrocytes where it replicates to produce invasive merozoites, which eventually egress to repeat the cycle. Merozoite surface protein-1 (MSP1), a prime malaria vaccine candidate and one of the most abundant components of the merozoite surface, is implicated in the ligand–receptor interactions leading to invasion. MSP1 is extensively proteolytically modified, first just before egress and then during invasion. These primary and secondary processing events are mediated respectively, by two parasite subtilisin-like proteases, PfSUB1 and PfSUB2, but the function and biological importance of the processing is unknown. Here, we examine the regulation and significance of MSP1 processing. We show that primary processing is ordered, with the primary processing site closest to the C-terminal end of MSP1 being cleaved last, irrespective of polymorphisms throughout the rest of the molecule. Replacement of the secondary processing site, normally refractory to PfSUB1, with a PfSUB1-sensitive site, is deleterious to parasite growth. Our findings show that correct spatiotemporal regulation of MSP1 maturation is crucial for the function of the protein and for maintenance of the parasite asexual blood-stage life cycle.

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“…Immunization of monkeys with native or recombinant MSP1 result in partial or complete protection against challenge infections (7,9,11,14,15,17,(30)(31)(32)36). MSP1 is synthesized as a 195-kDa precursor polypeptide and 83-, 42-, fragments are proteolytically processed from the 195-kDa molecule (10,13,16,18,25). The precursor polypeptide and its processing fragments are present on the surface of free merozoites.…”

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confidence: 99%

Immunological cross-reactivity of the C-terminal 42-kilodalton fragment of Plasmodium falciparum merozoite surface protein 1 expressed in baculovirus

et al. 1993

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The roles of allelic and conserved epitopes in vaccine-induced immunity to the C-terminal 42-kDa fragment of the Plasmodiumfalc4ium merozoite surface protein 1 (MSP1) were investigated. The C-terminal fragment of MSP1 was expressed as a baculovirus recombinant protein, BVp42. Rabbits were immunized with BVp42, and antibodies were tested for reactivity to MSP1s of the homologous and heterologous allelic forms, represented by the FUP, FVO, FC27, and Honduras parasite isolates, by enzyme-linked immunosorbent assay and indirect immunofluorescence antibody assay. Despite the fact that allelic sequences accounted for * Corresponding author.

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The N-terminal amino acid sequences of the Plasmodium falciparum (FCB1) merozoite surface antigens of 42 and 36 kilodalton, both derived from the 185–195-kilodalton precursor

Cited by 21 publications

References 37 publications

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Regulated maturation of malaria merozoite surface protein‐1 is essential for parasite growth

Immunological cross-reactivity of the C-terminal 42-kilodalton fragment of Plasmodium falciparum merozoite surface protein 1 expressed in baculovirus

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