Article (Scientific journals)
Apolipoprotein L-I is the trypanosome lytic factor of human serum.
Vanhamme, Luc; Paturiaux-Hanocq, Francoise; Poelvoorde, Philippe et al.
2003In Nature, 422 (6927), p. 83-7
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Keywords :
Animals; Apolipoproteins/blood/chemistry/metabolism; Disease Susceptibility; Endocytosis; Humans; Lipoproteins, HDL/blood/chemistry/metabolism; Lysosomes/metabolism; Membrane Glycoproteins/chemistry/genetics/metabolism; Models, Molecular; Protein Binding; Protozoan Proteins; Trypanosoma brucei rhodesiense/metabolism/pathogenicity
Abstract :
[en] Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal alpha-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal alpha-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vanhamme, Luc
Paturiaux-Hanocq, Francoise
Poelvoorde, Philippe
Nolan, Derek P
Lins, Laurence  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Van Den Abbeele, Jan
Pays, Annette
Tebabi, Patricia
Van Xong, Huang
Jacquet, Alain
Moguilevsky, Nicole
Dieu, Marc
Kane, John P
De Baetselier, Patrick
Brasseur, Robert ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Pays, Etienne
More authors (6 more) Less
Language :
English
Title :
Apolipoprotein L-I is the trypanosome lytic factor of human serum.
Publication date :
2003
Journal title :
Nature
ISSN :
0028-0836
eISSN :
1476-4687
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
Volume :
422
Issue :
6927
Pages :
83-7
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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