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MSP1  -  merozoite surface protein 1 precursor

Plasmodium falciparum 3D7

Synonyms: MSA1, MSP-1, PMMSA, Pf190, merozoite surface antigen 1
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Disease relevance of PFI1475w

  • Although G17.12 was raised against the recombinant antigen expressed in an insect cell/baculovirus system, it binds uniformly to the surface of merozoites from the late schizont stage, showing that the cognate epitope is exposed on the naturally occurring MSP1 polypeptide complex [1].
  • In an attempt to produce a product that is easily scaleable and inexpensive, we expressed the C-terminal 42 kDa of MSP1 (MSP1(42)) in Escherichia coli, refolded the protein to its native form from insoluble inclusion bodies, and tested its ability to elicit antibodies with in vitro and in vivo activities [2].
  • These results suggest that clinical symptoms occurring during falciparum malaria seem to be associated with the development of levels of antibody against particular epitopes on MSP1, which is under the control of an immunoregulatory mechanism [3].
  • The 28-day follow-up period was used coupled with PCR genotyping for MSP1 and MSP2 in order to differentiate recrudescence from re-infections for parasites that appeared after Day 14 [4].
  • We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia [5].

Psychiatry related information on PFI1475w

  • Various aspects of MSP-1 processing including immunological and physiological reactions in the host during the critical period of schizogony can now be examined in vivo [6].

High impact information on PFI1475w

  • Our results suggest that an effective MSP-119-based falciparum malaria vaccine should aim to induce an antibody response that prevents MSP-1 processing on the merozoite surface [7].
  • Most significantly, affinity-purified, naturally acquired human antibodies specific for epitopes within the NH2-terminal 83-kD domain of MSP-1 very effectively block the processing-inhibitory activity of the anti-MSP-119 mAb 12 [7].
  • This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes [8].
  • The major surface protein MSP-1 of Plasmodium falciparum blood-stage malaria parasites contains notably conserved sequence blocks with unknown function [9].
  • These findings suggest that the chymotrypsin-sensitive MSP1-band 3 interaction plays a role in a sialic acid-independent invasion pathway and reveal the function of MSP1 in the Plasmodium invasion of RBCs [10].

Biological context of PFI1475w

  • In this study, we have used biochemical approaches to identify the binding sites within MSP1 and MSP9 involved in the co-ligand complex formation [11].
  • Induction of antibodies to the Plasmodium falciparum merozoite surface protein-1 (MSP1) by cross-priming with heterologous MSP1s [12].
  • In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP1(19)) were assessed [13].
  • This preferential recognition of conserved epitopes of MSP1 was confirmed by competitive binding ELISAs [14].
  • Finally and of particular interest, in the case of MSP1, the antibody response appears to be strongly potentiated by the presence of additional plasmids, indicating an adjuvant effect of DNA [15].

Anatomical context of PFI1475w

  • Our evidence suggests a ternary complex is formed between MSP1, MSP9, and band 3 during erythrocyte invasion by P. falciparum [11].
  • The relative importance of these sequences in providing T cell help for Ab production was investigated in a series of cross-priming studies using homologous and heterologous parasite MSP1 proteins [12].
  • Dominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys [14].
  • MSP1 is anchored to the merozoite plasma membrane in vivo by a glycosyl-phosphatidyl-inositol (GPI) moiety, implicated in malaria pathology [16].
  • Synthetic chimeric DNA constructs with a reduced A + T content coding for full-length merozoite surface protein-1 of Plasmodium falciparum (MSP1) and three fragments thereof were expressed in HeLa cells [17].

Associations of PFI1475w with chemical compounds

  • We propose that suramin and related compounds inhibit erythrocyte invasion by binding to MSP1 and by preventing its cleavage by the secondary processing protease [18].
  • Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1 [19].
  • In addition, direct sequencing of 31 isolates confirmed reported sequence substitutions in the C-terminal 19-kDa Cys-rich region of MSP1, supporting a notion of limited variations in this region, a strong vaccine candidate molecule [20].
  • Isolates of Plasmodium falciparum from patients in a Sudanese village exhibiting RI resistance to chloroquine have been typed for allelic variants of 2 merozoite surface antigens, MSP1 and MSP2 [21].
  • The antigen tested was the merozoite surface glycoprotein 1 (MSP1) of Plasmodium falciparum, a vaccine candidate targeting the asexual erythrocytic stage [22].

Other interactions of PFI1475w

  • MSP8 is a recently identified merozoite surface protein that shares similar structural features with the leading vaccine candidate MSP1 [23].
  • MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype [24].
  • In Plasmodium falciparum, merozoite surface protein 7 (MSP7) was originally identified as a 22kDa protein on the merozoite surface and associated with the MSP1 complex shed during erythrocyte invasion [25].
  • Remarkably, this cleavage is mediated by the same membrane-bound parasite serine protease as that responsible for shedding of the merozoite surface protein-1 (MSP-1) complex, an abundant, glycosylphosphatidylinositol-anchored multiprotein complex [26].
  • We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP-2 alleles and S-antigen sequence types, at the end of a long period of low transmission [27].

Analytical, diagnostic and therapeutic context of PFI1475w


  1. Crystal structure of a Fab complex formed with PfMSP1-19, the C-terminal fragment of merozoite surface protein 1 from Plasmodium falciparum: a malaria vaccine candidate. Pizarro, J.C., Chitarra, V., Verger, D., Holm, I., Pêtres, S., Dartevelle, S., Nato, F., Longacre, S., Bentley, G.A. J. Mol. Biol. (2003) [Pubmed]
  2. Biochemical and immunological characterization of bacterially expressed and refolded Plasmodium falciparum 42-kilodalton C-terminal merozoite surface protein 1. Singh, S., Kennedy, M.C., Long, C.A., Saul, A.J., Miller, L.H., Stowers, A.W. Infect. Immun. (2003) [Pubmed]
  3. Epitope-specific impairment of production of antibody against merozoite surface glycoprotein 1 of Plasmodium falciparum in symptomatic patients with malaria. Fu, J., Hato, M., Ohmae, H., Matsuoka, H., Kawabata, M., Tanabe, K., Miyamoto, Y., Leafasia, J.L., Chinzei, Y., Ohta, N. Parasitol. Res. (2000) [Pubmed]
  4. Assessment of the therapeutic efficacy of a paediatric formulation of artemether-lumefantrine (Coartesiane(R)) for the treatment of uncomplicated Plasmodium falciparum in children in Zambia. Chanda, P., Hawela, M., Kango, M., Sipilanyambe, N. Malar. J. (2006) [Pubmed]
  5. Azurin, Plasmodium falciparum malaria and HIV/AIDS: inhibition of parasitic and viral growth by Azurin. Chaudhari, A., Fialho, A.M., Ratner, D., Gupta, P., Hong, C.S., Kahali, S., Yamada, T., Haldar, K., Murphy, S., Cho, W., Chauhan, V.S., Das Gupta, T.K., Chakrabarty, A.M. Cell Cycle (2006) [Pubmed]
  6. Processing of the Plasmodium chabaudi chabaudi AS merozoite surface protein 1 in vivo and in vitro. O'Dea, K.P., McKean, P.G., Harris, A., Brown, K.N. Mol. Biochem. Parasitol. (1995) [Pubmed]
  7. Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies. Guevara Patiño, J.A., Holder, A.A., McBride, J.S., Blackman, M.J. J. Exp. Med. (1997) [Pubmed]
  8. Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. Blackman, M.J., Scott-Finnigan, T.J., Shai, S., Holder, A.A. J. Exp. Med. (1994) [Pubmed]
  9. A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrin. Herrera, S., Rudin, W., Herrera, M., Clavijo, P., Mancilla, L., de Plata, C., Matile, H., Certa, U. EMBO J. (1993) [Pubmed]
  10. Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Goel, V.K., Li, X., Chen, H., Liu, S.C., Chishti, A.H., Oh, S.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  11. Two Plasmodium falciparum merozoite proteins binding to erythrocyte band 3 form a direct complex. Kariuki, M.M., Li, X., Yamodo, I., Chishti, A.H., Oh, S.S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  12. Induction of antibodies to the Plasmodium falciparum merozoite surface protein-1 (MSP1) by cross-priming with heterologous MSP1s. Hui, G.S., Hashimoto, A.C., Nikaido, C.M., Choi, J., Chang, S.P. J. Immunol. (1994) [Pubmed]
  13. Human leukocyte antigen class II alleles influence levels of antibodies to the Plasmodium falciparum asexual-stage apical membrane antigen 1 but not to merozoite surface antigen 2 and merozoite surface protein 1. Johnson, A.H., Leke, R.G., Mendell, N.R., Shon, D., Suh, Y.J., Bomba-Nkolo, D., Tchinda, V., Kouontchou, S., Thuita, L.W., van der Wel, A.M., Thomas, A., Stowers, A., Saul, A., Zhou, A., Taylor, D.W., Quakyi, I.A. Infect. Immun. (2004) [Pubmed]
  14. Dominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys. Hui, G.S., Nikaido, C., Hashiro, C., Kaslow, D.C., Collins, W.E. Infect. Immun. (1996) [Pubmed]
  15. Multi-plasmid DNA vaccination avoids antigenic competition and enhances immunogenicity of a poorly immunogenic plasmid. Grifantini, R., Finco, O., Bartolini, E., Draghi, M., Del Giudice, G., Kocken, C., Thomas, A., Abrignani, S., Grandi, G. Eur. J. Immunol. (1998) [Pubmed]
  16. Soluble and glyco-lipid modified baculovirus Plasmodium falciparum C-terminal merozoite surface protein 1, two forms of a leading malaria vaccine candidate. Bonnet, S., Pêtres, S., Holm, I., Fontaine, T., Rosario, S., Roth, C., Longacre, S. Vaccine (2006) [Pubmed]
  17. Analysis of recombinant merozoite surface protein-1 of Plasmodium falciparum expressed in mammalian cells. Burghaus, P.A., Gerold, P., Pan, W., Schwarz, R.T., Lingelbach, K., Bujard, H. Mol. Biochem. Parasitol. (1999) [Pubmed]
  18. Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum. Fleck, S.L., Birdsall, B., Babon, J., Dluzewski, A.R., Martin, S.R., Morgan, W.D., Angov, E., Kettleborough, C.A., Feeney, J., Blackman, M.J., Holder, A.A. J. Biol. Chem. (2003) [Pubmed]
  19. Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. Blackman, M.J., Holder, A.A. Mol. Biochem. Parasitol. (1992) [Pubmed]
  20. Plasmodium falciparum: allelic variation in the merozoite surface protein 1 gene in wild isolates from southern Vietnam. Kaneko, O., Kimura, M., Kawamoto, F., Ferreira, M.U., Tanabe, K. Exp. Parasitol. (1997) [Pubmed]
  21. Genetic evidence that RI chloroquine resistance of Plasmodium falciparum is caused by recrudescence of resistant parasites. Babiker, H., Ranford-Cartwright, L., Sultan, A., Satti, G., Walliker, D. Trans. R. Soc. Trop. Med. Hyg. (1994) [Pubmed]
  22. A simple screening method for detecting bindings between oligopeptides and HLA-DR molecules on filter papers: possible application for mapping of putative helper T-cell epitopes on MSP1 of Plasmodium falciparum. Fu, J., Hato, M., Igarashi, K., Suzuki, T., Matsuoka, H., Ishii, A., Leafasia, J.L., Chinzei, Y., Ohta, N. Microbiol. Immunol. (2000) [Pubmed]
  23. MSP8 is a non-essential merozoite surface protein in Plasmodium falciparum. Black, C.G., Wu, T., Wang, L., Topolska, A.E., Coppel, R.L. Mol. Biochem. Parasitol. (2005) [Pubmed]
  24. Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity. Eisen, D.P., Saul, A., Fryauff, D.J., Reeder, J.C., Coppel, R.L. Am. J. Trop. Med. Hyg. (2002) [Pubmed]
  25. Extensive proteolytic processing of the malaria parasite merozoite surface protein 7 during biosynthesis and parasite release from erythrocytes. Pachebat, J.A., Kadekoppala, M., Grainger, M., Dluzewski, A.R., Gunaratne, R.S., Scott-Finnigan, T.J., Ogun, S.A., Ling, I.T., Bannister, L.H., Taylor, H.M., Mitchell, G.H., Holder, A.A. Mol. Biochem. Parasitol. (2007) [Pubmed]
  26. A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage. Howell, S.A., Well, I., Fleck, S.L., Kettleborough, C., Collins, C.R., Blackman, M.J. J. Biol. Chem. (2003) [Pubmed]
  27. Limited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal Kenya. Kyes, S., Harding, R., Black, G., Craig, A., Peshu, N., Newbold, C., Marsh, K. Am. J. Trop. Med. Hyg. (1997) [Pubmed]
  28. Immunity to recombinant plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Singh, S., Miura, K., Zhou, H., Muratova, O., Keegan, B., Miles, A., Martin, L.B., Saul, A.J., Miller, L.H., Long, C.A. Infect. Immun. (2006) [Pubmed]
  29. Comparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoelii. Tian, J.H., Kumar, S., Kaslow, D.C., Miller, L.H. Infect. Immun. (1997) [Pubmed]
  30. Construction of a tetR-integrated Salmonella enterica serovar Typhi CVD908 strain that tightly controls expression of the major merozoite surface protein of Plasmodium falciparum for applications in human Vaccine production. Qian, F., Pan, W. Infect. Immun. (2002) [Pubmed]
  31. Protective immune responses to the 42-kilodalton (kDa) region of Plasmodium yoelii merozoite surface protein 1 are induced by the C-terminal 19-kDa region but not by the adjacent 33-kDa region. Ahlborg, N., Ling, I.T., Howard, W., Holder, A.A., Riley, E.M. Infect. Immun. (2002) [Pubmed]
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