The ''Plasmodium'' helical interspersed subtelomeric proteins (PHIST) or ring-infected erythrocyte surface antigens (RESA) are a

family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its ...

of protein domains found in the

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

-causing ''

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...

'' species. It was initially identified as a short four-helical conserved region in the single-domain export proteins, but the identification of this part associated with a

DnaJ In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans. Function Molecular chaperones are a diverse family o ...

domain in ''P. falciparum'' RESA (named after the ring stage of the parasite) has led to its reclassification as the RESA N-terminal domain. This domain has been classified into three subfamilies, PHISTa, PHISTb, and PHISTc. The PHIST proteins are exported to the cytoplasm of the infected erythrocyte. The human malaria parasites ''

P. falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...

'' and '' P. vivax'' have shown a lineage-specific expansion of proteins with this domain. Of the two PHIST genes in the mouse parasite '' P. berghei'', only one is required for infection. The PHIST domain folds into three long helices (forming a

bundle Bundle or Bundling may refer to: * Bundling (packaging), the process of using straps to bundle up items Biology * Bundle of His, a collection of heart muscle cells specialized for electrical conduction * Bundle of Kent, an extra conduction pat ...

) and two smaller N-terminal helices, and is monomeric in solution. It binds

PfEMP1 ''Plasmodium falciparum'' erythrocyte membrane protein 1 (PfEMP1) is a family of proteins present on the membrane surface of red blood cells (RBCs or erythrocytes) that are infected by the malarial parasite ''Plasmodium falciparum''. PfEMP1 is ...

ATS C-terminus and plays a role in "knob" formation.

RESA

The full RESA protein in ''P. falciparum'' also contains a few other domains, namely the DnaJ domain and the DnaJ-associated X domain. A part of the X-domain, RESA/P13830_663-670, appears to bind and reinforce spectrin cytoskeleton so that each erythrocyte only hosts one parasite. ''P. falciparum'' isolate 3D7 encodes three RESA-family proteins, RESA-1 (P13830//PF3D7_0102200), RESA-2 (M91672.1//PF3D7_1149500), RESA-3 (/PF3D7_1149200). RESA-2 is usually considered a transcribed pseudogene due to a premature stop codon. However, a missense mutation T1526G or T1526C in RESA-2 that removes this stop codon is commly found. It is associated with increased severity of disease.

Notes

References

{{reflist Protein domains Helical interspersed subtelomeric protein Antigens Apicomplexan proteins