Malaria sporozoites and circumsporozoite protein bind sulfated glycans: carbohydrate binding properties predicted from sequence homologies with other lectins.
Circumsporozoite (CS) proteins, the major surface proteins of the sporozoites of the various malaria (Plasmodium) species, share a region of highly conserved sequence homology in common with sporozoite surface protein 2 (SSP2) and a group of proteins observed to specifically bind sulfated glycoconjugates. Recombinant P. yoelii CS protein was found to bind selectively to heparin-, fucoidan-, and dextran sulfate-Sepharose, but poorly to chondroitin sulfate A- or C-Sepharose. It also bound with lower affinity to a heparan sulfate biosynthesis-deficient mutant cell line compared with the wild-type. Likewise, P. berghei sporozoite invasion into hepatocytes was selectively inhibited by fucoidan, heparin, and dextran sulfate, and sporozoites bound specifically to sulfatide [galactosyl (3-SO4) beta 1-1 ceramide] coated surfaces. Sporozoite infectivity in mice was significantly inhibited by dextran sulfate 500,000 and fucoidan. Taken together, these data indicate that CS proteins bind selectively to certain sulfated glyconjugates and invasion of host hepatocytes by sporozoites, and sporozoite infectivity can be inhibited by such compounds.
Pancake
S J
SJ
Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5055.
Holt
G D
GD
Mellouk
S
S
Hoffman
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016264:Dextran Sulfate / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006001:Glycoconjugates / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008288:Malaria / Q000517:prevention & control; D051379:Mice; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D006001:Glycoconjugates; D006017:Glycolipids; D011134:Polysaccharides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan; D006493:Heparin; D016264:Dextran Sulfate; C007789:fucoidan