A potential novel mechanism for the insertion of a membrane protein revealed by a biochemical analysis of the Plasmodium falciparum cytoadherence molecule PfEMP-1.
Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is exposed on the surface of infected erythrocytes where it both acts as an important pathogenicity factor in malaria and undergoes antigenic variation as a means of immune evasion. Because the mammalian erythrocyte lacks a protein secretory machinery there has been much interest in elucidating the mechanism whereby this protein is transferred from its site of synthesis within the parasite to its final destination. Current opinion favours a mechanism whereby PfEMP-1 becomes cotranslationally inserted into the endoplasmic reticulum of the parasite and is subsequently transported as an integral part of an erythrocyte cytoplasmic membrane system derived from the parasite. Here we show that the solubility characteristics of this protein during several stages of its transport pathway are inconsistent with this view. Instead we propose that the protein is synthesized as a peripheral membrane protein which only when it arrives at its final destination assumes a transmembrane topology. Even in this state, the extractability of the protein with urea suggest that it is anchored in the membrane by protein-protein rather than by protein-lipid interaction.
Papakrivos
Janni
J
FB Biology, Philipps-University Marburg, 35032 Marburg, Germany.
Newbold
Chris I
CI
Lingelbach
Klaus
K
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D004910:Erythrocyte Membrane / Q000469:parasitology; D006801:Humans; D008322:Mammals; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000469:parasitology
D008565:Membrane Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum