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首页> 外文期刊>Biochemistry >Analysis of the sequence motifs responsible for the interactions of peroxins 14 and 5, which are involved in glycosome biogenesis in Trypanosoma brucei.
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Analysis of the sequence motifs responsible for the interactions of peroxins 14 and 5, which are involved in glycosome biogenesis in Trypanosoma brucei.

机译：分析引起过氧化物酶14和5相互作用的序列基序，过氧化物酶14和5与布鲁氏锥虫的糖体生物发生有关。

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Glycosome biogenesis in trypanosomatids occurs via a process that is homologous to peroxisome biogenesis in other eukaryotes. Glycosomal matrix proteins are synthesized in the cytosol and imported posttranslationally. The import process involves a series of protein-protein interactions starting by recognition of glycosomal matrix proteins by a receptor in the cytosol. Most proteins to be imported contain so-called PTS-1 or PTS-2 targeting sequences recognized by, respectively, the receptor proteins PEX5 and PEX7. PEX14, a protein associated with the peroxisomal membrane, has been identified as a component of the docking complex and a point of convergence of the PEX5- and PEX7-dependent import pathways. In this paper, the strength of the interactions between Trypanosoma brucei PEX14 and PEX5 was studied by a fluorescence assay, using (i) a panel of N-terminal regions of TbPEX14 protein variants and (ii) a series of different peptides derived from TbPEX5, each containing one of the three WXXXF/Y motifs present in this receptor protein. On the PEX14 side, the N-terminal region of TbPEX14 including residues 1-84 appeared to be responsible for TbPEX5 binding. The results from PEX14 mutants identified specific residues in the N-terminal region of TbPEX14 involved in PEX5 binding and showed that in particular hydrophobic residues F35 and F52 are critical. On the PEX5 side, 13-mer peptides incorporating the first or the third WXXXF/Y motif bind to PEX14 with an affinity in the nanomolar range. However, the second WXXXF/Y motif peptide did not show any detectable affinity. Studies using variants of second and third motif peptides suggest that the alpha-helical content of the peptides as well as the charge of a residue at position 9 in the motif may be important for PEX14 binding. Assays with 7-, 10-, 13-, and 16-mer third motif peptides showed that 16-mers and 13-mers have comparable binding affinity for PEX14, whereas 10-mers and 7-mers have about 10- and 100-fold lower affinity than the 16-mers, respectively. The low sequence identities of PEX14 and PEX5 between parasite and its human host, and the vital importance of proper glycosome biogenesis to the parasite, render these peroxins highly promising drug targets.
机译：锥虫的糖体生物发生是通过与其他真核生物中过氧化物酶体生物发生同源的过程发生的。糖体基质蛋白在细胞质中合成并翻译后导入。导入过程涉及一系列蛋白质-蛋白质相互作用，首先是通过胞浆中的受体识别糖体基质蛋白。大多数要输入的蛋白质均包含所谓的PTS-1或PTS-2靶向序列，分别被受体蛋白PEX5和PEX7识别。 PEX14是一种与过氧化物酶体膜相关的蛋白质，已被确定为对接复合物的组成部分，是PEX5和PEX7依赖的进口途径的汇合点。在本文中，使用（i）TbPEX14蛋白变体的N端区域和（ii）一系列源自TbPEX5的不同肽，通过荧光分析研究了布鲁氏锥虫PEX14和PEX5之间的相互作用强度。每个包含该受体蛋白中存在的三个WXXXF / Y基序之一。在PEX14一侧，包含残基1-84的TbPEX14的N端区域似乎负责TbPEX5的结合。 PEX14突变体的结果确定了TbPEX14 N末端区域中参与PEX5结合的特定残基，并显示特别是疏水残基F35和F52是至关重要的。在PEX5一侧，掺入第一个或第三个WXXXF / Y基序的13-mer肽以纳摩尔范围的亲和力与PEX14结合。但是，第二个WXXXF / Y基序肽未显示任何可检测的亲和力。使用第二个和第三个基序肽的变体进行的研究表明，肽的α-螺旋含量以及基序中9位残基的电荷对于PEX14结合可能很重要。用7个，10个，13个和16个mer的第三基序肽进行的测定表明16个mer和13个mers对PEX14具有相当的结合亲和力，而10个mer和7个mer具有约10倍和100倍亲和力分别低于16聚体。 PEX14和PEX5在寄生虫及其人类宿主之间的低序列同一性，以及正确的糖体生物合成对寄生虫的至关重要性，使这些过氧化物酶成为极有希望的药物靶标。

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