Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) destabilizes erythrocyte membrane skeleton.
Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) is a parasite-derived protein that appears on the cytoplasmic surface of the host cell membrane in the later stages of the parasite's development where it associates with membrane skeleton. We have recently demonstrated that a 60-residue fragment (FIa1, residues 38-97) of PfEMP3 bound to spectrin. Here we show that this polypeptide binds specifically to a site near the C terminus of alpha-spectrin at the point that spectrin attaches to actin and protein 4.1R in forming the junctions of the membrane skeletal network. We further show that this polypeptide disrupts formation of the ternary spectrin-actin-4.1R complex in solution. Importantly, when incorporated into the cell, the PfEMP3 fragment causes extensive reduction in shear resistance of the cell. We conjecture that the loss of mechanical cohesion of the membrane may facilitate the exit of the mature merozoites from the cell.
Pei
Xinhong
X
Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065.
Guo
Xinhua
X
Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065.
Coppel
Ross
R
Department of Microbiology, Monash University, Monash, Victoria 3800, Australia.
Mohandas
Narla
N
Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065.
An
Xiuli
X
Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065. Electronic address: xan@nybloodcenter.org.
D000818:Animals; D001665:Binding Sites; D001696:Biomechanical Phenomena; D019281:Dimerization; D004910:Erythrocyte Membrane / Q000737:chemistry*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D015800:Protozoan Proteins / Q000737:chemistry / Q000502:physiology*; D013049:Spectrin / Q000737:chemistry
C411566:EMP3 protein, Plasmodium falciparum; C438245:Fla1 protein, Trypanosoma; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; D013049:Spectrin