Galland Nathalie, de Walque Stéphane, Voncken Frank G J, Verlinde Christophe L M J, Michels Paul A M
Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, TROP 74.39, Avenue Hippocrate 74, B-1200 Brussels, Belgium.
Mol Biochem Parasitol. 2010 May;171(1):45-9. doi: 10.1016/j.molbiopara.2010.01.002. Epub 2010 Feb 4.
In kinetoplastid protists, glycolysis is compartmentalized in glycosomes, organelles belonging to the peroxisome family. The Trypanosoma brucei glycosomal enzyme triosephosphate isomerase (TPI) does not contain either of the two established peroxisome-targeting signals, but we identified a 22 amino acids long fragment, present at an internal position of the polypeptide, that has the capacity to route a reporter protein to glycosomes in transfected trypanosomes, as demonstrated by cell-fractionation experiments and corroborating immunofluorescence studies. This polypeptide-internal routing information seems to be unique for the sequence of the trypanosome enzyme: a reporter protein fused to a Saccharomyces cerevisiae peptide containing the sequence corresponding to the 22-residue fragment of the T. brucei enzyme, was not targeted to glycosomes. In yeasts, as in most other organisms, TPI is indeed exclusively present in the cytosol. These results suggest that it may be possible to develop new trypanocidal drugs by targeting specifically the glycosome import mechanism of TPI.
在动质体原生生物中，糖酵解被分隔在糖体中，糖体是属于过氧化物酶体家族的细胞器。布氏锥虫的糖体酶磷酸丙糖异构酶（TPI）不包含已确定的两种过氧化物酶体靶向信号中的任何一种，但我们鉴定出了一个位于多肽内部位置的22个氨基酸长的片段，细胞分级分离实验和免疫荧光研究证实，该片段能够将报告蛋白引导至转染锥虫中的糖体。这种多肽内部的引导信息似乎对于锥虫酶的序列是独特的：与含有对应于布氏锥虫酶22个残基片段序列的酿酒酵母肽融合的报告蛋白，并未靶向至糖体。在酵母中，与大多数其他生物体一样，TPI确实仅存在于细胞质中。这些结果表明，有可能通过特异性靶向TPI的糖体导入机制来开发新的杀锥虫药物。
