title: Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC).
abstract: Plasmodium vivax is one of four Plasmodium species that cause human malaria. P. vivax and a related simian malaria parasite, Plasmodium knowlesi, invade erythrocytes by binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy binding proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy binding proteins of P. vivax (PvDBP) and P. knowlesi (PkDaBP) with DARC-expressing cells. These sulphated tyrosines also participate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to phenylalanine interferes with the association of IL8 with DARC. A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at residue 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of many or most chemokines with their receptors, and identify a key molecular determinant of erythrocyte invasion by P. vivax.
authors.affiliation: Perlmutter Laboratory, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hyeryun
authors.initials: H
authors.lastname: Choe
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Owens
authors.forename: Paulette L
authors.initials: PL
authors.lastname: Wright
authors.forename: Natalya
authors.initials: N
authors.lastname: Vasilieva
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Agam P
authors.initials: AP
authors.lastname: Singh
authors.forename: Rushdi
authors.initials: R
authors.lastname: Shakri
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D004375:Duffy Blood-Group System / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D010966:Plasmodium vivax / Q000276:immunology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D014443:Tyrosine