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
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Research Support, Non-U.S. Gov't
MeSH terms
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
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Amino Acid Sequence
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Animals
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Anions / metabolism
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Apolipoprotein L1
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Apolipoproteins / chemistry*
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Apolipoproteins / genetics
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Apolipoproteins / metabolism*
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Apolipoproteins / pharmacology
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Cells, Immobilized
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Chlorides / metabolism
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Colicins / chemistry
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Colicins / pharmacology
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Escherichia coli / drug effects
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Escherichia coli / growth & development
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Humans
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Intracellular Membranes / drug effects
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Intracellular Membranes / metabolism*
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Intracellular Membranes / ultrastructure
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Ion Channels / metabolism
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Lipid Bilayers / chemistry
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Lipoproteins, HDL / chemistry*
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Lipoproteins, HDL / genetics
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Lipoproteins, HDL / metabolism*
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Lipoproteins, HDL / pharmacology
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Lysosomes / drug effects
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Lysosomes / metabolism*
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Lysosomes / ultrastructure
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Permeability
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / metabolism
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Trypanosoma brucei brucei / drug effects
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Trypanosoma brucei brucei / metabolism*
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Trypanosoma brucei brucei / ultrastructure
Substances
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APOL1 protein, human
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Anions
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Apolipoprotein L1
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Apolipoproteins
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Chlorides
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Colicins
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Ion Channels
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Lipid Bilayers
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Lipoproteins, HDL
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Recombinant Proteins
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid