The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion

Alida Coppi, Consuelo Pinzon-Ortiz, Christina Hutter, Photini Sinnis

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalJournal of Experimental Medicine
Issue number1
StatePublished - Jan 3 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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