Plasmodium helical interspersed subtelomeric protein

The Plasmodium helical interspersed subtelomeric proteins (PHIST) or ring-infected erythrocyte surface antigens (RESA) are a family of protein domains found in the malaria-causing Plasmodium species. It was initially identified as a short four-helical conserved region in the single-domain export proteins,^[1] but the identification of this part associated with a DnaJ 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.^[2]

Plasmodium RESA, N-terminal
Identifiers
Symbol	PRESAN
Pfam	PF09687
InterPro	IPR019111
CATH	4jle
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary
Also IPR006526. The structure is chain-swapped: each side of the blue line is a "solution" monomer.

The PHIST proteins are exported to the cytoplasm of the infected erythrocyte. The human malaria parasites P. falciparum and P. vivax have shown a lineage-specific expansion of proteins with this domain.^[1] Of the two PHIST genes in the mouse parasite P. berghei, only one is required for infection.^[3] The PHIST domain folds into three long helices (forming a bundle) and two smaller N-terminal helices, and is monomeric in solution. It binds PfEMP1 ATS C-terminus and plays a role in "knob" formation.^[4]

RESA

Ring-infected erythrocyte surface antigen
Identifiers
Organism	Plasmodium falciparum FC27/Papua New Guinea
Symbol	RESA
Alt. symbols	Pf155, RESA-1
UniProt	P13830
Search for Structures Swiss-model Domains InterPro

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.^[5]

P. falciparum isolate 3D7 encodes three RESA-family proteins, RESA-1 (P13830/Q8I0U6/PF3D7_0102200), RESA-2 (M91672.1/UPI0000084FE4/PF3D7_1149500), RESA-3 (Q8IHN1/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.^[6][7]

Notes