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PMID: 15630135 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion.

The Journal of experimental medicine ·Vol. 201 ·No. 1 ·2005-01-03 ·Pages 27-33

Coppi A, Pinzon-Ortiz C, Hutter C, Sinnis P

Abstract

The circumsporozoite protein (CSP) is the major surface protein of Plasmodium sporozoites, the infective stage of malaria. Although CSP has been extensively studied as a malaria vaccine candidate, little is known about its structure. Here, we show that CSP is proteolytically cleaved by a papain family cysteine protease of parasite origin. Our data suggest that the highly conserved region I, found just before the repeat region, contains the cleavage site. Cleavage occurs on the sporozoite surface when parasites contact target cells. Inhibitors of CSP processing inhibit cell invasion in vitro, and treatment of mice with E-64, a highly specific cysteine protease inhibitor, completely inhibits sporozoite infectivity in vivo.

MeSH Terms
Amino Acid Sequence Animals Cysteine Endopeptidases/metabolism Cysteine Proteinase Inhibitors/pharmacology Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Immunoblotting Immunoprecipitation Leucine/analogs & derivatives,pharmacology Malaria/prevention & control Molecular Sequence Data Peptides/genetics,metabolism Plasmodium/metabolism,pathogenicity Protozoan Proteins/metabolism Sporozoites/metabolism,pathogenicity Virulence/drug effects
Chemicals
Cysteine Proteinase Inhibitors Peptides Protozoan Proteins circumsporozoite protein, Protozoan Cysteine Endopeptidases Leucine E 64
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Coppi Alida
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
Pinzon-Ortiz Consuelo
Hutter Christina
Sinnis Photini
References (27)
27 references, click to expand
  1. Sporozoite antigens: biology and immunology of the circumsporozoite protein and thrombospondin-related anonymous protein.
    Chem Immunol. 2002;80:70-96 PMID: 12058652
  2. Cutting edge: a new tool to evaluate human pre-erythrocytic malaria vaccines: rodent parasites bearing a hybrid Plasmodium falciparum circumsporozoite protein.
    J Immunol. 2002 Dec 15;169(12):6681-5 PMID: 12471098
  3. Cysteine proteases of parasitic organisms.
    Mol Biochem Parasitol. 2002 Mar;120(1):1-21 PMID: 11849701
  4. Detection of malaria liver-stages in mice infected through the bite of a single Anopheles mosquito using a highly sensitive real-time PCR.
    Int J Parasitol. 2001 Nov;31(13):1499-502 PMID: 11595237
  5. Proteolytic processing and primary structure of Plasmodium falciparum apical membrane antigen-1.
    J Biol Chem. 2001 Aug 17;276(33):31311-20 PMID: 11399764
  6. Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets.
    Curr Drug Targets. 2000 Jul;1(1):59-83 PMID: 11475536
  7. The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for plasmodium sporozoite attachment to target cells.
    J Biol Chem. 2001 Jul 20;276(29):26784-91 PMID: 11352923
  8. Fluorescent Plasmodium berghei sporozoites and pre-erythrocytic stages: a new tool to study mosquito and mammalian host interactions with malaria parasites.
    Cell Microbiol. 2001 Jun;3(6):371-9 PMID: 11422080
  9. Migration of Plasmodium sporozoites through cells before infection.
    Science. 2001 Jan 5;291(5501):141-4 PMID: 11141568
  10. Cysteine protease inhibitors as chemotherapy for parasitic infections.
    Bioorg Med Chem. 1999 Apr;7(4):639-44 PMID: 10353643
  11. The involvement of cysteine proteases and protease inhibitor genes in the regulation of programmed cell death in plants.
    Plant Cell. 1999 Mar;11(3):431-44 PMID: 10072402
  12. Characterization of membrane-associated Clostridium perfringens enterotoxin following pronase treatment.
    Infect Immun. 1998 Dec;66(12):5897-905 PMID: 9826371
  13. Plasmodium vivax: a monoclonal antibody recognizes a circumsporozoite protein precursor on the sporozoite surface.
    Exp Parasitol. 1998 Nov;90(3):203-11 PMID: 9806864
  14. Proteases of malaria parasites: new targets for chemotherapy.
    Emerg Infect Dis. 1998 Jan-Mar;4(1):49-57 PMID: 9452398
  15. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
    Protein Eng. 1997 Jan;10(1):1-6 PMID: 9051728
  16. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes.
    Nature. 1997 Jan 23;385(6614):336-40 PMID: 9002517
  17. Circumsporozoite protein of Plasmodium gallinaceum characterized by monoclonal antibodies.
    Parasite Immunol. 1988 Sep;10(5):523-33 PMID: 2461541
  18. Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs.
    Nature. 1988 Sep 1;335(6185):82-5 PMID: 3045564
  19. Characterization of Plasmodium yoelii monoclonal antibodies directed against stage-specific sporozoite antigens.
    Infect Immun. 1987 Mar;55(3):604-8 PMID: 2434426
  20. Reaction of serine proteases with substituted isocoumarins: discovery of 3,4-dichloroisocoumarin, a new general mechanism based serine protease inhibitor.
    Biochemistry. 1985 Apr 9;24(8):1831-41 PMID: 3893537
  21. Monoclonal antibodies identify the protective antigens of sporozoites of Plasmodium knowlesi.
    Proc Natl Acad Sci U S A. 1982 Sep;79(18):5651-5 PMID: 6957883
  22. Circumsporozoite proteins of human malaria parasites Plasmodium falciparum and Plasmodium vivax.
    J Exp Med. 1982 Jul 1;156(1):20-30 PMID: 7045272
  23. Biosynthesis of Pb44, the protective antigen of sporozoites of Plasmodium berghei.
    J Exp Med. 1981 Oct 1;154(4):1225-36 PMID: 7026723
  24. Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite.
    Science. 1980 Jan 4;207(4426):71-3 PMID: 6985745
  25. Role of proteases in host cell invasion by Toxoplasma gondii and other Apicomplexa.
    Acta Trop. 2004 Jun;91(1):69-81 PMID: 15158690
  26. Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite.
    Genome Res. 2003 Apr;13(4):601-16 PMID: 12671001
  27. Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein.
    J Biol Chem. 2002 Mar 1;277(9):7092-8 PMID: 11751898
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20040989
Published
2005-01-03
Pages
27-33
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC1995445
Subset
IM
Grants
NIAID NIH HHS · 5T32 AI07180 · United States
NIAID NIH HHS · R01 AI056840 · United States
NIAID NIH HHS · R01 AI044470 · United States
NIAID NIH HHS · R01 AI44470 · United States
NIAID NIH HHS · T32 AI007180 · United States
External Links
PubMed source DOI: 10.1084/jem.20040989 PMC Full Text View journal details
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