PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1

FEBS J. 2018 Jan;285(2):294-312. doi: 10.1111/febs.14340. Epub 2017 Dec 10.

Abstract

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family.

Keywords: PHIST; Plasmodium falciparum; PfEMP-1; PfSBP-1; infected RBCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Carrier Proteins / metabolism
  • Cell Adhesion
  • Chromatography, Gel
  • Membrane Proteins / metabolism
  • Organelles / metabolism*
  • Phosphorylation
  • Plasmodium falciparum / metabolism
  • Plasmodium falciparum / pathogenicity*
  • Polymorphism, Genetic
  • Protein Binding
  • Protozoan Proteins / genetics
  • Protozoan Proteins / isolation & purification
  • Protozoan Proteins / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Subcellular Fractions / metabolism*
  • Virulence Factors / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Pfsbp1 protein, Plasmodium falciparum
  • Protozoan Proteins
  • Recombinant Proteins
  • Virulence Factors
  • erythrocyte membrane protein 1, Plasmodium falciparum