The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum

Genome Biol. 2005;6(3):R26. doi: 10.1186/gb-2005-6-3-r26. Epub 2005 Mar 2.

Abstract

Background: The uptake of nutrients, expulsion of metabolic wastes and maintenance of ion homeostasis by the intraerythrocytic malaria parasite is mediated by membrane transport proteins. Proteins of this type are also implicated in the phenomenon of antimalarial drug resistance. However, the initial annotation of the genome of the human malaria parasite Plasmodium falciparum identified only a limited number of transporters, and no channels. In this study we have used a combination of bioinformatic approaches to identify and attribute putative functions to transporters and channels encoded by the malaria parasite, as well as comparing expression patterns for a subset of these.

Results: A computer program that searches a genome database on the basis of the hydropathy plots of the corresponding proteins was used to identify more than 100 transport proteins encoded by P. falciparum. These include all the transporters previously annotated as such, as well as a similar number of candidate transport proteins that had escaped detection. Detailed sequence analysis enabled the assignment of putative substrate specificities and/or transport mechanisms to all those putative transport proteins previously without. The newly-identified transport proteins include candidate transporters for a range of organic and inorganic nutrients (including sugars, amino acids, nucleosides and vitamins), and several putative ion channels. The stage-dependent expression of RNAs for 34 candidate transport proteins of particular interest are compared.

Conclusion: The malaria parasite possesses substantially more membrane transport proteins than was originally thought, and the analyses presented here provide a range of novel insights into the physiology of this important human pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Animals
  • Computational Biology / methods
  • Equilibrative Nucleoside Transport Proteins / genetics
  • Equilibrative Nucleoside Transport Proteins / metabolism
  • Erythrocytes / parasitology
  • Genomics
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Malaria, Falciparum / parasitology
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / physiology
  • Molecular Sequence Data
  • Multigene Family / genetics
  • Multigene Family / physiology
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / metabolism
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / physiology
  • RNA, Protozoan / metabolism
  • Sequence Alignment

Substances

  • Amino Acid Transport Systems
  • Equilibrative Nucleoside Transport Proteins
  • Ion Channels
  • Membrane Transport Proteins
  • Protozoan Proteins
  • RNA, Protozoan