A Single Amino Acid Substitution in the Group 1 Trypanosoma brucei gambiense Haptoglobin-Hemoglobin Receptor Abolishes TLF-1 Binding

被引:39
作者
DeJesus, E. [1 ]
Kieft, R. [1 ]
Albright, B. [1 ]
Stephens, N. A. [1 ]
Hajduk, S. L. [1 ]
机构
[1] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA
关键词
RESISTANCE-ASSOCIATED PROTEIN; LYTIC FACTOR; INNATE IMMUNITY; HUMAN-SERUM; MECHANISM; COMPLEX; ROLES; LYSIS; GENE;
D O I
10.1371/journal.ppat.1003317
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1). This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR) on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT), escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR) mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.
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页数:10
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