An additional primary proteolytic processing site in merozoite surface protein-1 of Plasmodium berghei

Wiser, Mark F.; Toebe, Carole S; Jennings, Gregory J.

doi:10.1016/s0166-6851(96)02811-3

Cited by 4 publications

(6 citation statements)

References 21 publications

(24 reference statements)

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“…), is indispensable in the asexual life cycle of the parasite. All Plasmodium species possess orthologues of MSP1, and the protein is subjected to a similar two-step proteolytic processing in all those species where the phenomenon has been examined (O'Dea et al, 1995;Blackman et al, 1996;Wiser et al, 1997;Jennings et al, 1998). Small molecules or antibodies that inhibit PfSUB1 activity or interfere with PfSUB2-mediated shedding of the MSP1/ 6/7 complex can prevent invasion Fleck et al, 2003;Koussis et al, 2009), leading to suggestions that proteolytic maturation of MSP1 is essential for invasion.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…At the time of merozoite differentiation the large precursor is proteolytically processed into smaller fragments [3] that form a noncovalent polypeptide complex [4]. There are three primary proteolytic processing sites in MSP-1 from P. falciparum, whereas MSP-1 from rodent parasites has four sites [5,6]. The sequences around the scissile bonds are somewhat conserved, suggesting that a single protease is responsible for the primary processing [6].…”

Section: Introductionmentioning

confidence: 99%

“…There are three primary proteolytic processing sites in MSP-1 from P. falciparum, whereas MSP-1 from rodent parasites has four sites [5,6]. The sequences around the scissile bonds are somewhat conserved, suggesting that a single protease is responsible for the primary processing [6]. At the time of merozoite invasion MSP-1 undergoes a secondary protease processing by a Ca 2 + -activated serine protease [7,8].…”

Section: Introductionmentioning

confidence: 99%

The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

Jennings

Toebe

Belkum

et al. 1998

Molecular and Biochemical Parasitology

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The complete gene for merozoite surface protein-1 (MSP-1) from Plasmodium berghei has been cloned and sequenced. Comparison of the P. berghei MSP-1 sequence with MSP-1 from other rodent parasites reveals five conserved domains interrupted by four variable blocks. These variable blocks exhibit no sequence homology but do have similar amino acid compositions. Primary proteolytic processing sites are located near the boundaries between the conserved domains and the variable blocks. Sequencing of the variable blocks from several P. berghei isolates shows that the predominant intra-species difference is in the number of tandem repeats. The inter-and intra-species differences suggest that the variable blocks are localized areas with relatively high levels of slipped-strand mispairing, unequal crossing-over, or other intragenic recombination activity. MSP-1 from P. berghei exhibits more repetitiveness than MSP-1 from other species suggesting that P. berghei experiences a higher intrinsic level of events producing variable numbers of tandem repeats or a lower level of events leading to the degeneration of tandem repeats.

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“…Prior reports have provided partial sequences of this protein from a related strain (K173) as well as from the ANKA strain. 28,29 In the former case, the sequence data are in complete agreement; there are a few discrepancies in the latter sequence beginning near nucleotide 700. The reasons for this are not known.…”

Section: Resultsmentioning

confidence: 74%

Cloning and characterization of the merozoite surface antigen 1 gene of Plasmodium berghei.

Zhong¹,

Fan²,

Yang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Merozoite surface antigen 1 (MSA1) is a promising candidate for vaccine development against malaria parasites. Here, we report the complete nucleotide sequence of the gene encoding the precursor to this major surface antigen of Plasmodium berghei strain ANKA using cDNA library screening and polymerase chain reaction techniques. A single open reading frame of 5,376 basepairs encoding a protein with a calculated molecular mass of 197 kD was defined. The protein contains a putative signal peptide of 19 amino acids, a membrane anchor sequence of 18 residues, and shows two epidermal growth factor-like domains rich in Cys residues at the C-terminus. There are four repeat sequences of oligopeptides in the molecule: tetrapeptide (Ser-Thr-Thr-Thr), tripeptide (Pro-Thr-Pro and Pro-Ala-Ala), and dipeptide (Ser-Gly). Furthermore, three nine-residue stretches of a motif (Ala-Ser-Asn-Pro-Gly-Ala-Ser-Ala-Ser) are located near each other. All of these repeat sequences are unexceptionally located in the variable regions when compared with other MSA1 molecules. The molecule displays 79% overall identity to the analogous antigen of P. yoelii yoelii strain YM, 70% to that of P. chabaudi chabaudi strain AS, and 38% to that of P. falciparum strain Wellcome.

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An additional primary proteolytic processing site in merozoite surface protein-1 of Plasmodium berghei

Cited by 4 publications

References 21 publications

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

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

The complete sequence of Plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability

Cloning and characterization of the merozoite surface antigen 1 gene of Plasmodium berghei.

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