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An unexpected extended conformation for the third TPR motif of the peroxinPEX5 from Trypanosoma brucei

机译:布鲁氏锥虫过氧化物酶PEX5的第三个TPR基序的意外扩展构象

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摘要

A number of helix-rich protein motifs are involved in a variety of critical protein-protein interactions in living cells. One of these is the tetratrico peptide repeat (TPR) motif that is involved, amongst others, in cell cycle regulation, chaperone function and post-translation modifications. So far, these helix-rich TPR motifs have always been observed to be a compact unit of two helices interacting with each other in antiparallel fashion. Here, we describe the structure of the first three TPR-motifs of the peroxin PEX5 from Trypanosoma brucei, the causative agent of sleeping sickness. Peroxins are proteins involved in peroxisome, glycosome and glyoxysome biogenesis. PEX5 is the receptor of the proteins targeted to these organelles by the "peroxisomal targeting signal-1", a C-terminal tripeptide called PTS-1. The first two of the three TPR-motifs of T.brucei PEX5 appear to adopt the canonical antiparallel helix hairpin structure. In contrast, the third TPR motif of PEX5 has a dramatically different conformation in our crystals: the two helices that were supposed to form a hairpin are folded into one single 44 Angstrom long continuous helix. Such a conformation has never been observed before for a TPR motif. This raises interesting questions including the potential functional importance of a "jack-knife" conformational change in TPR motifs.
机译:许多富含螺旋的蛋白质基序参与活细胞中的各种关键蛋白质-蛋白质相互作用。其中之一是四三肽重复序列(TPR),它尤其参与细胞周期调节,分子伴侣功能和翻译后修饰。到目前为止,一直以来都观察到这些富含螺旋的TPR图案是两个以反平行方式彼此相互作用的螺旋的紧凑单元。在这里,我们描述了来自昏睡的锥虫锥虫过氧化物酶PEX5的前三个TPR基序的结构。过氧化物酶是涉及过氧化物酶体,糖体和乙醛酸体生物发生的蛋白质。 PEX5是通过“过氧化物酶体靶向信号1”(称为PTS-1的C端三肽)靶向这些细胞器的蛋白质的受体。 T.brucei PEX5的三个TPR基序中的前两个似乎采用规范的反平行螺旋发夹结构。相比之下,PEX5的第三个TPR基序在我们的晶体中具有截然不同的构象:应该将形成发夹的两个螺旋折叠成一个单个的44埃长的连续螺旋。 TPR基序从未见过这种构象。这提出了有趣的问题,包括TPR图案中“千刀”构象变化的潜在功能重要性。

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