TY - JOUR
T1 - The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion
AU - Coppi, Alida
AU - Pinzon-Ortiz, Consuelo
AU - Hutter, Christina
AU - Sinnis, Photini
PY - 2005/1/3
Y1 - 2005/1/3
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20040989
DO - 10.1084/jem.20040989
M3 - Article
C2 - 15630135
AN - SCOPUS:12344299732
SN - 0022-1007
VL - 201
SP - 27
EP - 33
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -