Plasmodium falciparum histidine-rich protein 1 associates with the band 3 binding domain of ankyrin in the infected red cell membrane.
Infection of erythrocytes by the malaria parasite Plasmodium falciparum results in the export of several parasite proteins into the erythrocyte cytoplasm. Changes occur in the infected erythrocyte due to altered phosphorylation of proteins and to novel interactions between host and parasite proteins, particularly at the membrane skeleton. In erythrocytes, the spectrin based red cell membrane skeleton is linked to the erythrocyte plasma membrane through interactions of ankyrin with spectrin and band 3. Here we report an association between the P. falciparum histidine-rich protein (PfHRP1) and phosphorylated proteolytic fragments of red cell ankyrin. Immunochemical, biochemical and biophysical studies indicate that the 89 kDa band 3 binding domain and the 62 kDa spectrin-binding domain of ankyrin are co-precipitated by mAb 89 against PfHRP1, and that native and recombinant ankyrin fragments bind to the 5' repeat region of PfHRP1. PfHRP1 is responsible for anchoring the parasite cytoadherence ligand to the erythrocyte membrane skeleton, and this additional interaction with ankyrin would strengthen the ability of PfEMP1 to resist shear stress.
Magowan
C
C
Lawrence Berkeley National Laboratory Life Sciences Division, Berkeley, CA 94720, USA.
Nunomura
W
W
Waller
K L
KL
Yeung
J
J
Liang
J
J
Van Dort
H
H
Low
P S
PS
Coppel
R L
RL
Mohandas
N
N
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D017487:Ankyrins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D004910:Erythrocyte Membrane / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000097:blood*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000378:metabolism*
D001457:Anion Exchange Protein 1, Erythrocyte; D017487:Ankyrins; D010455:Peptides; D010750:Phosphoproteins; D015800:Protozoan Proteins; C042968:knob protein, Plasmodium falciparum