title: Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperone complexes within the host erythrocyte.
abstract: Malaria parasites modify their host cell, the mature human erythrocyte. We are interested in the molecules mediating these processes, and have recently described a family of parasite-encoded heat shock proteins (PfHsp40s) that are targeted to the host cell, and implicated in host cell modification. Hsp40s generally function as co-chaperones of members of the Hsp70 family, and until now it was thought that human Hsp70 acts as the PfHsp40 interaction partner within the host cell. Here we revise this hypothesis, and identify and characterize an exported parasite-encoded Hsp70, referred to as PfHsp70-x. PfHsp70-x is exported to the host erythrocyte where it forms a complex with PfHsp40s in structures known as J-dots, and is closely associated with PfEMP1. Interestingly, Hsp70-x is encoded only by parasite species that export the major virulence factor EMP1, implying a possible role for Hsp70-x in EMP1 presentation at the surface of the infected erythrocyte. Our data strongly support the presence of parasite-encoded chaperone/co-chaperone complexes within the host erythrocyte, which are involved in protein traffic through the host cell. The host-pathogen interaction within the infected erythrocyte is more complex than previously thought, and is driven notonly by parasite co-chaperones, but also by the parasite-encoded chaperone Hsp70-x itself.
authors.affiliation: Parasitology, Philipps University Marburg, Marburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Külzer
authors.forename: Sarah
authors.initials: S
authors.lastname: Charnaud
authors.forename: Tal
authors.initials: T
authors.lastname: Dagan
authors.forename: Jan
authors.initials: J
authors.lastname: Riedel
authors.forename: Pradipta
authors.initials: P
authors.lastname: Mandal
authors.forename: Eva R
authors.initials: ER
authors.lastname: Pesce
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gilson
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
mesh_terms: D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004912:Erythrocytes / Q000737:chemistry* / Q000469:parasitology*; D050956:HSP40 Heat-Shock Proteins / Q000032:analysis*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011485:Protein Binding; D055503:Protein Multimerization; D021381:Protein Transport; D015800:Protozoan Proteins / Q000032:analysis*; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum