Structural and functional properties of region II-plus of the malaria circumsporozoite protein

Photini Sinnis, Pedro Clavijo, David Fenyö, Brian T. Chait, Carla Cerami, Victor Nussenzweig

Research output: Contribution to journalArticle

Abstract

During feeding, infected mosquitos inject malaria sporozoites into the host circulation. Within minutes, the parasites are found in the liver where they initiate the first stage of malaria infection. All species of malaria sporozoites are uniformly covered by the circumsporozoite protein (CS), which contains a conserved COOH-terminal sequence called region II-plus. We have previously shown that region II-plus is the parasite's hepatocyte-binding ligand and that this ligand binds to heparan sulfate proteoglycans (HSPGs) on the hepatocyte membrane. Using a series of substituted region II-plus peptides, we show here that the downstream basic amino acids as well as the interdispersed hydrophobic residues are required for binding of CS to hepatocyte HSPGs. We also show that this positively charged stretch of amino acids must be aggregated in order to bind to the receptor. On the basis of this information, we have synthesized a multiple antigen peptide that mimics the hepatocyte-binding ligand. This construct inhibits both CS binding to HepG2 cells in vitro as well as CS clearance in mice.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalJournal of Experimental Medicine
Volume180
Issue number1
DOIs
StatePublished - Jul 1 1994
Externally publishedYes

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Malaria
Hepatocytes
Sporozoites
Heparan Sulfate Proteoglycans
Ligands
Parasites
Proteins
Basic Amino Acids
Peptides
Hep G2 Cells
Culicidae
Protein Binding
Carrier Proteins
Antigens
Amino Acids
Membranes
Liver
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Structural and functional properties of region II-plus of the malaria circumsporozoite protein. / Sinnis, Photini; Clavijo, Pedro; Fenyö, David; Chait, Brian T.; Cerami, Carla; Nussenzweig, Victor.

In: Journal of Experimental Medicine, Vol. 180, No. 1, 01.07.1994, p. 297-306.

Research output: Contribution to journalArticle

Sinnis, Photini ; Clavijo, Pedro ; Fenyö, David ; Chait, Brian T. ; Cerami, Carla ; Nussenzweig, Victor. / Structural and functional properties of region II-plus of the malaria circumsporozoite protein. In: Journal of Experimental Medicine. 1994 ; Vol. 180, No. 1. pp. 297-306.
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