This family contains sexual stage s48/45 antigens from Plasmodium (approximately 450 residues long). These are surface proteins expressed by Plasmodium male and female gametes that have been shown to play a conserved and important role in fertilisation (PUBMED:11163248).
The 6-Cysteine (6-Cys) domain is found in Plasmodium proteins that are expressed in all stages of the parasite life cycle in both the vertebrate and mosquito hosts. The domain is of roughly 120 amino acids and contains six positionally conserved cysteines. It might occur in 1-14 copies per protein, either as the sole globular domain or in combination wih beta-helix-forming hexapeptide repeats as is the case of sequestrin. It is generally found in tandem pairs of A-type and B-type domains. Previously believed to be exclusive to Plasmodium, the 6-Cys domain also exists in proteins found in all members of the aconoidasidan (hematozoan) clade of Apicomplexa, which unites the haemosporidians (Plasmodium) and piroplasms) [ (PUBMED:11163248) (PUBMED:16155126) (PUBMED:20386715) (PUBMED:22493233) (PUBMED:23511632) ].
The 6-cys domain is a beta-sandwich formed by two sheets with a mixture of parallel and antiparallel strands. Three disulfide bonds are present in the 6_Cys domain with C1-C2, C3-C6, and C4-C5 connectivity. C1-C2 and C3-C6 pin together the two sheets of the beta-sandwich, whereas C4-C5 links an ancyllary loop to the core domain [ (PUBMED:22493233) (PUBMED:23511632) ].
Some Plasmodium proteins known to contain a 6-Cys domain are listed below:
Pfs48/45, involved in male/female gamete fusion in the mosquito midgut. It is predicted to be glycosylphosphatidylinositol (GPI)-anchored to the gamete surface.
Pfs230, involved in male/female gamete fusion in the mosquito midgut. It is a soluble protein that associates with the gamete membrane by binding to Pfs48/45.
Pfs47, involved in male/female gamete fusion in the mosquito midgut. It is found on female gametes.
P52, expressed in the sporozoite. May be required for invasion of hepatocytes and to promote normal development in the liver.
P36, expressed in the sporozoite. May be required for invasion of hepatocytes and to promote normal development in the liver.
Pf41, located on the surface of merozoites and has a signal sequence.
Pf38, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.
Pf12, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.
Pf92, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.
Family alignment:
There are 1287 s48_45 domains in 509 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing s48_45 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with s48_45 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing s48_45 domain in the selected taxonomic class.
A central role for P48/45 in malaria parasite male gamete fertility.
Cell. 2001; 104: 153-64
Display abstract
Fertilization and zygote development are obligate features of the malariaparasite life cycle and occur during parasite transmission to mosquitoes.The surface protein PFS48/45 is expressed by male and female gametes ofPlasmodium falciparum and PFS48/45 antibodies prevent zygote developmentand transmission. Here, gene disruption was used to show that Pfs48/45 andthe ortholog Pbs48/45 from a rodent malaria parasite P. berghei play aconserved and important role in fertilization. p48/45- parasites had areduced capacity to produce oocysts in mosquitoes due to greatly reducedzygote formation. Unexpectedly, only male gamete fertility of p48/45-parasites was affected, failing to penetrate otherwise fertile femalegametes. P48/45 is shown to be a surface protein of malaria parasites witha demonstrable role in fertilization.
