Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum.
Ps230 is the largest representative of a 10-member family of proteins found in all Plasmodium species. The family is defined by partially conserved, cysteine-rich double domains that are approximately 350 aa in length and have one to three predicted disulfide bridges in each half. In Plasmodium falciparum, the most dangerous human malaria, Pf12 is the smallest member of the family, comprising just one double domain. Pfs230, with 7 double domains, and Pfs48/45 and Pfs47, with 1.5 double domains each, are found on the gamete surfaces and are thus potential candidates for a transmission-blocking vaccine. Fold prediction analyses of the double domains in Pfs230 reveal structural resemblance to SAG1 (surface antigen 1), a surface protein with a double beta-sandwich structure from another apicomplexan parasite, Toxoplasma gondii. Template-directed modeling onto SAG1 clearly establishes the structural link between SAG1 and Pfs230 and produces positions for the cysteines that accord with the disulfide-bonding arrangement predicted for the Pfs230 family in earlier work. A highly clustered region of polymorphisms within the second double domain in Pfs230 maps to one side of the sandwich surface. This observation suggests that this region may be functional and reinforces the validity of these molecular models for the core domains of the Pfs230 family of proteins.
Gerloff
Dietlind L
DL
Institute of Structural and Molecular Biology, University of Edinburgh, EH9 3JR Edinburgh, United Kingdom. d.gerloff@ed.ac.uk
Creasey
Alison
A
Maslau
Siarhei
S
Carter
Richard
R
D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry*; D005854:Germ Cells; D008562:Membrane Glycoproteins / Q000737:chemistry; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D014122:Toxoplasma / Q000737:chemistry
D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; C430263:Pfs230 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; C047168:SAG1 antigen, Toxoplasma; C084847:pfs48-45 protein, Plasmodium falciparum