Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes

Science. 2005 Jul 15;309(5733):469-72. doi: 10.1126/science.1114566.

Abstract

Apolipoprotein L-I is the trypanolytic factor of human serum. Here we show that this protein contains a membrane pore-forming domain functionally similar to that of bacterial colicins, flanked by a membrane-addressing domain. In lipid bilayer membranes, apolipoprotein L-I formed anion channels. In Trypanosoma brucei, apolipoprotein L-I was targeted to the lysosomal membrane and triggered depolarization of this membrane, continuous influx of chloride, and subsequent osmotic swelling of the lysosome until the trypanosome lysed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Amino Acid Sequence
  • Animals
  • Anions / metabolism
  • Apolipoprotein L1
  • Apolipoproteins / chemistry*
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism*
  • Apolipoproteins / pharmacology
  • Cells, Immobilized
  • Chlorides / metabolism
  • Colicins / chemistry
  • Colicins / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / ultrastructure
  • Ion Channels / metabolism
  • Lipid Bilayers / chemistry
  • Lipoproteins, HDL / chemistry*
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, HDL / pharmacology
  • Lysosomes / drug effects
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Permeability
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / metabolism
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / metabolism*
  • Trypanosoma brucei brucei / ultrastructure

Substances

  • APOL1 protein, human
  • Anions
  • Apolipoprotein L1
  • Apolipoproteins
  • Chlorides
  • Colicins
  • Ion Channels
  • Lipid Bilayers
  • Lipoproteins, HDL
  • Recombinant Proteins
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid