The merozoite surface protein 1 complex of human malaria parasite Plasmodium falciparum: interactions and arrangements of subunits.
The major protein component at the surface of merozoites, the infectious form of blood stage malaria parasites, is the merozoite surface protein 1 (MSP-1) complex. In the human malaria parasite Plasmodium falciparum, this complex is generated by proteolytic cleavage of a 190-kDa glycosylphosphatidylinositol-anchored precursor into four major fragments, which remain non-covalently associated. Here, we describe the in vitro reconstitution of the MSP-1 complex of P. falciparum strain 3D7 from its heterologously produced subunits. We provide evidence for the arrangement of the subunits within the complex and show how they interact with each other. Our data indicate that the conformation assumed by the reassembled complex as well as by the heterologously produced 190-kDa precursor corresponds to the native one. Based on these results we propose a first structural model for the MSP-1 complex. Together with access to faithfully produced material, this information will advance further structure-function studies of MSP-1 that plays an essential role during invasion of erythrocytes by the parasite and that is considered a promising candidate for a malaria vaccine.
Kauth
Christian W
CW
Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Epp
Christian
C
Bujard
Hermann
H
Lutz
Rolf
R
D000818:Animals; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000032:analysis* / Q000737:chemistry; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010963:Plasmodium falciparum / Q000235:genetics*; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D013917:Thrombin / Q000378:metabolism
D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D021122:Protein Subunits; D011994:Recombinant Proteins; D013917:Thrombin