title: P-selectin is a host receptor for Plasmodium MSP7 ligands.
abstract: BACKGROUND
  Plasmodium parasites typically elicit a non-sterile but protective immune response in human host populations, suggesting that the parasites actively modulate normal immunological mechanisms. P-selectin is a cell surface receptor expressed in mammals, that is a known component of the inflammatory response against pathogens and has been previously identified as a host factor that influences malaria-associated pathology both in human patients and rodent infection models.
  
  
  METHODS
  To better understand the molecular mechanisms underlying the involvement of P-selectin in the pathogenesis of malaria, a systematic extracellular protein interaction screen was used to identify Plasmodium falciparum merozoite surface protein 7 (MSP7) as a binding partner of human P-selectin. This interaction, and those occurring between P-selectin and Plasmodium MSP7 homologues, was characterized biochemically.
  
  
  RESULTS
  Plasmodium falciparum MSP7 and P-selectin were shown to bind each other directly via the N-terminus of PfMSP7 and the P-selectin C-type lectin and EGF-like domains. Orthologous proteins in the murine parasite Plasmodium berghei (PbMSRP1 and PbMSRP2) and mouse P-selectin also interacted. Finally, P-selectin, when complexed with MSP7, could no longer bind to its endogenous carbohydrate ligand, Sialyl-Lewis(X).
  
  
  CONCLUSIONS
  Novel interactions were identified between Plasmodium MSP7 protein family members and host P-selectin receptors. Since PfMSP7 could prevent interactions between P-selectin and its leukocyte ligands, these results provide a possible mechanism for the known immunomodulatory effects of both MSP7 and P-selectin in malaria infection models.
authors.affiliation: Cell Surface Signalling Laboratory and Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ap11@sanger.ac.uk.
authors.forename: Abigail J
authors.initials: AJ
authors.lastname: Perrin
authors.affiliation: Cell Surface Signalling Laboratory and Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. jb28@sanger.ac.uk.
authors.forename: S Josefin
authors.initials: SJ
authors.lastname: Bartholdson
authors.affiliation: Cell Surface Signalling Laboratory and Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. gw2@sanger.ac.uk.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
mesh_terms: D000818:Animals; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism*; D019007:P-Selectin / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
chemical_list: D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D009844:Oligosaccharides; D019007:P-Selectin; D015800:Protozoan Proteins; C546937:SELP protein, human; D000080506:Sialyl Lewis X Antigen; C439571:merozoite surface protein 7, Plasmodium