Analysis of structure and function of the giant protein Pf332 in Plasmodium falciparum.
Virulence of Plasmodium falciparum, the most lethal parasitic disease in humans, results in part from adhesiveness and increased rigidity of infected erythrocytes. Pf332 is trafficked to the parasite-infected erythrocyte via Maurer's clefts, structures for protein sorting and export in the host erythrocyte. This protein has a domain similar to the Duffy-binding-like (DBL) domain, which functions by binding to receptors for adherence and invasion. To address structure of the Pf332 DBL domain, we expressed this region, and validated its fold on the basis of the disulphide bond pattern, which conformed to the generic pattern for DBL domains. The modelled structure for Pf332 DBL had differences compared with the erythrocyte-binding region of the alphaDBL domain of Plasmodium knowlesi Duffy-binding protein (Pk alpha-DBL). We addressed the function of Pf332 by constructing parasites that either lack expression of the protein or express an altered form. We found no evidence that Pf332 is involved in cytoadhesion or merozoite invasion. Truncation of Pf332 had a significant effect on deformability of the P. falciparum-infected erythrocyte, while loss of the full protein deletion did not. Our data suggest that Pf332 may contribute to the overall deformability of the P. falciparum-infected erythrocyte by anchoring and scaffolding.
Hodder
Anthony N
AN
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Maier
Alexander G
AG
Rug
Melanie
M
Brown
Monica
M
Hommel
Mirja
M
Pantic
Ivan
I
Puig-de-Morales-Marinkovic
Marina
M
Smith
Brian
B
Triglia
Tony
T
Beeson
James
J
Cowman
Alan F
AF
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D004912:Erythrocytes / Q000469:parasitology; D017353:Gene Deletion; D006801:Humans; D052940:Merozoites / Q000502:physiology; D008958:Models, Molecular; D010449:Peptide Mapping; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000502:physiology; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism* / Q000502:physiology; D013329:Structure-Activity Relationship
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C073415:antigen Pf332, Plasmodium