Hydrophobic interactions in Plasmodium falciparum invasion into human erythrocytes.
Human glycophorins block in vitro invasion of Plasmodium falciparum merozoites into human erythrocytes. A segment of glycophorin A which appears to be involved in the inhibition, is at, or adjacent to, the membrane-spanning domain of the molecule. To study the role of hydrophobic interactions in the inhibition, a series of proteins were derivatized with lipophilic side groups, and tested for inhibitory activity. Glycophorin A became five times more inhibitory after derivatization with nitrobenzylfurazan groups. Bovine serum albumin was derivatized to different degrees with nitrobenzylfurazan, dinitrobenzyl, trinitrobenzyl, dansyl, disulfonic stilbene, and fluorescein groups. The presence of hydrophobic side groups on the protein rendered it highly inhibitory to invasion, whereas the presence of hydrophilic substitutes such as disulfonic stilbenes did not. Other soluble proteins such as human serum albumin, transferrin, ovalbumin, fetuin and casein derivatized with dinitrobenzyl groups, were also found to block invasion. Inhibition was not a result of toxic effects of the protein derivatives on parasite metabolism or development. A minimum of ten hydrophobic side groups per bovine serum albumin was required in order to elicit appreciable inhibition. The invasion blocking activity was highly correlated with the rate and affinity of binding of the derivatized macromolecules to heptyl-Sepharose. The latter provided a quantitative measure for the capacity of amphiphiles to undergo hydrophobic interactions with insoluble matrices. The results of the present study indicate that hydrophobic interactions may be an essential component in the invasion of P. falciparum merozoites into human erythrocytes.
D000818:Animals; D001798:Blood Proteins / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology*; D006021:Glycophorins / Q000502:physiology*; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D007700:Kinetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000502:physiology*
D001798:Blood Proteins; D006021:Glycophorins; D007202:Indicators and Reagents; D012795:Sialoglycoproteins; D012710:Serum Albumin, Bovine