Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes.
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.
Pérez-Morga
David
D
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
Vanhollebeke
Benoit
B
Paturiaux-Hanocq
Françoise
F
Nolan
Derek P
DP
Lins
Laurence
L
Homblé
Fabrice
F
Vanhamme
Luc
L
Tebabi
Patricia
P
Pays
Annette
A
Poelvoorde
Philippe
P
Jacquet
Alain
A
Brasseur
Robert
R
Pays
Etienne
E
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000378:metabolism; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018914:Cells, Immobilized; D002712:Chlorides / Q000378:metabolism; D003087:Colicins / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007473:Ion Channels / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010539:Permeability; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
C108666:APOL1 protein, human; D000838:Anions; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D002712:Chlorides; D003087:Colicins; D007473:Ion Channels; D008051:Lipid Bilayers; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid