Mature parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum binds to the 30-kDa domain of protein 4.1 in malaria-infected red blood cells.
The Plasmodium falciparum mature parasite-infected erythrocyte surface antigen (MESA) is exported from the parasite to the infected red blood cell (IRBC) membrane skeleton, where it binds to protein 4.1 (4.1R) via a 19-residue MESA sequence. Using purified RBC 4.1R and recombinant 4.1R fragments, we show MESA binds the 30-kDa region of RBC 4.1R, specifically to a 51-residue region encoded by exon 10 of the 4.1R gene. The 3D structure of this region reveals that the MESA binding site overlaps the region of 4.1R involved in the p55, glycophorin C, and 4.1R ternary complex. Further binding studies using p55, 4.1R, and MESA showed competition between p55 and MESA for 4.1R, implying that MESA bound at the IRBC membrane skeleton may modulate normal 4.1R and p55 interactions in vivo. Definition of minimal binding domains involved in critical protein interactions in IRBCs may aid the development of novel therapies for falciparum malaria.
Waller
Karena L
KL
Department of Medicine (Cardiology), Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA. kwaller@aecom.yu.edu
Nunomura
Wataru
W
An
Xiuli
X
Cooke
Brian M
BM
Mohandas
Narla
N
Coppel
Ross L
RL
D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D010963:Plasmodium falciparum; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1