P. Ying et al., THE MALARIA CIRCUMSPOROZOITE PROTEIN - INTERACTION OF THE CONSERVED REGION-I AND REGION-II-PLUS WITH HEPARIN-LIKE OLIGOSACCHARIDES IN HEPARAN-SULFATE, Experimental parasitology, 85(2), 1997, pp. 168-182
The malaria circumsporozoite protein: Interaction of the conserved reg
ions I and II-plus with heparin-like oligosaccharides in heparan sulfa
te. Experimental Parasitology 85, 168-182. The malaria circumsporozoit
e (CS) protein binds to glycosaminoglycans from heparan sulfate proteo
glycans on the cell surface of hepatocytes and is specifically cleared
from the bloodstream by the liver. We show here that the two conserve
d regions, I and II-plus, of the CS protein, in a concerted action, pr
eferentially bind to highly sulfated heparin-like oligosaccharides in
heparan sulfate. In a concentration-dependent manner, peptides represe
nting region I and region II-plus inhibited the binding of recombinant
CS protein to HepG2 cells by 62 and 84%, respectively. Furthermore, t
he action of endoproteinase Arg-C, which cleaves the recombinant CS co
nstructs CS27IVC and CSFZ(Cys) predominantly at the conserved region I
, was inhibited by heparin in a concentration-dependent fashion. CSFZ(
Cys), which has a higher affinity to HSPGs than CS27IVC, was stabilize
d by heparin at a w/w ratio (CS protein:glycosaminoglycan) of 20/1, wh
ereas full protection of CS27IVC required more heparin (5/1). Heparan
sulfate provided full protection of CSFZ(Cys) only at a ratio of 1/10.
Native fucoidan as well as normally sulfated fuco-oligosaccharides (0
.76 mol sulfate/mol fucose) inhibited Plasmodium berghei development i
n HepG2 cells by 84 and 66%, respectively, in a concentration-dependen
t manner and sporozoite invasion into CHO cells by 80%. Desulfated fuc
oidan oligosaccharides were inactive. These results may explain the se
lective interaction between the CS protein and the unique heparan sulf
ate from liver, which is noted for its unusually high degree of sulfat
ion, and may provide a plausible explanation for the selective targeti
ng of the malaria CS protein to the liver. (C) 1997 Academic Press.