| Title | Haptoglobin-related protein mediates trypanosome lytic factor binding to trypanosomes. | | Author(s) | Drain J, Bishop JR, Hajduk SL | | Institution | Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, 35294, USA. | | Source | J Biol Chem 2001 Aug 10; 276(32):30254-60. | | MeSH | Animals
Antibodies, Monoclonal
Antigens, Neoplasm
Apolipoproteins
Binding, Competitive
Blood Proteins
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Haptoglobins
Humans
Kinetics
Ligands
Lipoproteins, HDL
Lysosomes
Microscopy, Fluorescence
Protein Binding
Research Support, U.S. Gov't, P.H.S.
Temperature
Trypanosoma brucei brucei
| | Abstract | Trypanosome lytic factor (TLF-1) is an unusual high density lipoprotein (HDL) found in human serum that is toxic to Trypanosoma brucei brucei and may be critical in preventing human infections by this parasite. TLF-1 is composed of four major apolipoproteins: apolipoprotein AI, apolipoprotein AII, paraoxonase, and the primate-specific haptoglobin-related protein (Hpr). Hpr is greater than 90% homologous to haptoglobin (Hp), an abundant acute phase serum protein. Killing of trypanosomes by TLF-1 requires cell surface binding, endocytosis, and subsequent lysosomal targeting. Low temperature binding studies reveal two receptors for TLF-1: one that is high affinity/low capacity (K(d) approximately 12 nm, 350 receptors per cell) and another that binds with low affinity/high capacity (K(d) approximately 1 microm, 60,000 receptors per cell). The low affinity binding is competed by nonlytic human HDL and is likely to be apolipoprotein AI-mediated. Purified human Hpr and human Hp bind to trypanosomes, are internalized, and are targeted to the lysosome. Furthermore, Hpr shows competition for TLF-1 binding, and a monoclonal antibody against Hpr prevents both TLF-1 uptake and trypanosome killing. Based on these results, we propose that Hpr mediates the high affinity binding of TLF-1 to T. b. brucei through a haptoglobin-like receptor. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11352898 |
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