Plasmodium RESA, N-terminal
InterproIPR019111
PfamPF09687
Cath4jle
BelowAlso . The structure is chain-swapped: each side of the blue line is a "solution" monomer.

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]

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
UniprotP13830
AltsymbolsPf155, RESA-1
OrganismPlasmodium falciparum FC27/Papua New Guinea

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/P13830663-670, 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//PF3D7_0102200), RESA-2 (M91672.1/UPI0000084FE4/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.[6][7]

References

  1. ^ Sargeant TJ, Marti M, Caler E, Carlton JM, Simpson K, Speed TP, Cowman AF (2006). "Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites". Genome Biology. 7 (2): R12. doi:10.1186/gb-2006-7-2-r12. PMC 1431722. PMID 16507167
  2. ^ Oakley MS, Kumar S, Anantharaman V, Zheng H, Mahajan B, Haynes JD, Moch JK, Fairhurst R, McCutchan TF, Aravind L (April 2007). "Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites". Infection and Immunity. 75 (4): 2012–25. doi:10.1128/IAI.01236-06. PMC 1865691. PMID 17283083
  3. ^ Moreira CK, Naissant B, Coppi A, Bennett BL, Aime E, Franke-Fayard B, Janse CJ, Coppens I, Sinnis P, Templeton TJ (29 March 2016). "The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites". PLOS ONE. 11 (3). Bibcode:2016PLoSO..1152510M. doi:10.1371/journal.pone.0152510. PMC 4811531. PMID 27022937
  4. ^ Oberli A, Slater LM, Cutts E, Brand F, Mundwiler-Pachlatko E, Rusch S, Masik MF, Erat MC, Beck HP, Vakonakis I (October 2014). "A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface". FASEB Journal. 28 (10): 4420–33. doi:10.1096/fj.14-256057. PMC 4202109. PMID 24983468
  5. ^ Pei X, Guo X, Coppel R, Bhattacharjee S, Haldar K, Gratzer W, Mohandas N, An X (August 2007). "The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum stabilizes spectrin tetramers and suppresses further invasion". Blood. 110 (3): 1036–42. doi:10.1182/blood-2007-02-076919. PMC 1924765. PMID 17468340
  6. ^ Badaut C, Guyonnet L, Milet J, Renard E, Durand R, Viwami F, Sagbo G, Layla F, Deloron P, Bonnefoy S, Migot-Nabias F (July 2015). "Immunoglobulin response to Plasmodium falciparum RESA proteins in uncomplicated and severe malaria". Malaria Journal. 14: 278. doi:10.1186/s12936-015-0799-8. PMC 4502540. PMID 26178656
  7. ^ Durand R, Migot-Nabias F, Andriantsoanirina V, Seringe E, Viwami F, Sagbo G, Lalya F, Deloron P, Mercereau-Puijalon O, Bonnefoy S (April 2012). "Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria". Malaria Journal. 11 (1): 128. doi:10.1186/1475-2875-11-128. PMC 3422168. PMID 22533816