Structural models for the protein family characterized by gamete surface protein Pfs230 ofPlasmodium falciparum

Abstract

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 Ϸ350 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 Pfs48͞45 and Pfs47, with 1.5 double domains each, are found on the gamete surfaces and are thus potential candidates for a transmissionblocking vaccine. Fold prediction analyses of the double domains in Pfs230 reveal structural resemblance to SAG1 (surface antigen 1), a surface protein with a double ␤-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.malaria ͉ protein structure prediction ͉ fertilization ͉ fold recognition ͉ transmission-blocking vaccine target

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

“…BLAST search identified the mosquito-stage protein PSOP12 (PFE0680) as paralog of CyRPA (69). This protein shares nine positionally conserved cysteine residues in the homologous N-terminal part, but additionally has a 6-cysteine-protein domain at the C terminus (70).…”

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

“…Self-recognition proteins have also been described for gamete fertilization in Plasmodium; namely, members of an amplified gene family which encodes glycophosphatidyl inositol (GPI)-linked proteins composed of 6-cys domains (Van Dijk et al 2010) and the HAP2 protein which functions in membrane fusion (Liu et al 2008). The 6-cys domain proteins are related to the Toxoplasma and Eimeria GPI-linked surface coat SAG proteins, and have been proposed to have originated via lateral transfer of metazoan ephrin proteins (Gerloff et al 2005;Arredondo et al 2012;Reid et al 2014). Ten members of the family are present in Plasmodium and appear to have roles in multiple stages of the lifecycle, including hepatocyte and intraerythrocytic stages (Ishino et al 2005;Sanders et al 2005;Annoura et al 2014).…”

Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium

“…Each domain typically contains 6 cysteines, likely paired in disulfide bridges, which is reminiscent of other cysteine-rich apicomplexan domains such as the COWP protein family of the oocyst wall in coccidians [26,27]; the 6-Cys family that includes the Plasmodium gamete proteins Pfs230, Pfs47 and Pfs48/45 [28][29][30][31]; and the Toxoplasma SAG proteins [28,30,31]. The cpw-wpc gene family is widely conserved among apicomplexans, including Table 3).…”