The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum stabilizes spectrin tetramers and suppresses further invasion.
The malaria parasite Plasmodium falciparum releases the ring-infected erythrocyte surface antigen (RESA) inside the red cell on entry. The protein migrates to the host cell membrane, where it binds to spectrin, but neither the nature of the interaction nor its functional consequences have previously been defined. Here, we identify the binding motifs involved in the interaction and describe a possible function. We have found that spectrin binds to a 108-amino acid fragment (residues 663-770) of RESA, and that this RESA fragment binds to repeat 16 of the beta-chain, close to the labile dimer-dimer self-association site. We further show that the RESA fragment stabilizes the spectrin tetramer against dissociation into its constituent dimers, both in situ and in solution. This is accompanied by enhanced resistance of the cell to both mechanical and thermal degradation. Resealed erythrocytes containing RESA(663-770) display resistance to invasion by merozoites of P falciparum. We infer that the evolutionary advantage of RESA to the parasite lies in its ability to prevent invasion of cells that are already host to a developing parasite, as well as possibly to guard the cell against thermal damage at the elevated body temperatures prevailing in febrile crises.
Pei
Xinhong
X
Red Cell Physiology Laboratory, New York Blood Center, 310 E. 67th Street, New York, NY 10021, USA.
Guo
Xinhua
X
Coppel
Ross
R
Bhattacharjee
Souvik
S
Haldar
Kasturi
K
Gratzer
Walter
W
Mohandas
Narla
N
An
Xiuli
X
D020816:Amino Acid Motifs; D000818:Animals; D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism* / Q000469:parasitology; D006358:Hot Temperature; D006801:Humans; D010963:Plasmodium falciparum / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D015800:Protozoan Proteins; D011994:Recombinant Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum; D013049:Spectrin