Targeting malaria virulence and remodeling proteins to the host erythrocyte

Science. 2004 Dec 10;306(5703):1930-3. doi: 10.1126/science.1102452.

Abstract

To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum. We identified 400 putative erythrocyte-targeted proteins corresponding to approximately 8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs*
  • Amino Acid Sequence
  • Animals
  • Computational Biology
  • Cytoplasm / metabolism
  • Erythrocyte Membrane / metabolism
  • Gene Expression Profiling
  • Genes, Protozoan
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Malaria, Falciparum / parasitology
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Plasmodium / chemistry
  • Plasmodium / genetics
  • Plasmodium / metabolism
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / pathogenicity*
  • Protein Sorting Signals*
  • Protein Transport
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Vacuoles / metabolism
  • Vacuoles / parasitology
  • Virulence
  • Virulence Factors / chemistry
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Membrane Proteins
  • Protein Sorting Signals
  • Protozoan Proteins
  • Recombinant Fusion Proteins
  • Virulence Factors