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首页> 外文期刊>Genes to cells : >Conserved aromatic and basic amino acid residues in the pore region of Caenorhabditis elegans spastin play critical roles in microtubule severing
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Conserved aromatic and basic amino acid residues in the pore region of Caenorhabditis elegans spastin play critical roles in microtubule severing

机译：秀丽隐杆线虫细孔区域中保守的芳香和碱性氨基酸残基在微管切断中起关键作用

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摘要

Mutations of human spastin, an AAA (ATPases associated with diverse cellular activity) family protein, cause an autosomal dominant form of hereditary spastic paraplegia, which is characterized by weakness, spasticity and loss of the vibratory sense in the lower limbs. Recently, it has been reported that spastin displays microtubule-severing activity. We also previously reported that Caenorhabditis elegans spastin homologue SPAS-1 displays microtubule severing. However, the detailed molecular mechanism of microtubule severing remains unknown. Here, we describe that SPAS-1 forms a stable hexamer in a concentration-dependent manner and that ATPase activity of SPAS-1 is greatly stimulated by microtubules. Furthermore, MTBD (microtubule-binding domain) of SPAS-1 is essential for binding to microtubules. Taken these results together, we propose that MTBD of SPAS-1 plays a critical role in enrichment of SPAS-1 to microtubules, where SPAS-1 is concentrated and able to form a stable hexamer, subsequently its ATPase activity is stimulated. On the other hand, our mutational analyses revealed that the conserved aromatic and basic amino acid residues in the pore region are important for microtubule severing. We also detected the direct interaction of the extremely acidic C-terminal polypeptide of tubulin with SPAS-1. Consequently, we propose that the central pore residues are important for the recognition of substrates.
机译：人类spastin（一种AAA（与多种细胞活性相关的ATP酶）家族蛋白）的突变会导致遗传性痉挛性截瘫的常染色体显性遗传，其特征是下肢无力，痉挛和振动感丧失。最近，据报道spastin显示出微管切断活性。我们以前也曾报道过秀丽隐杆线虫spastin同源物SPAS-1显示微管切断。然而，微管切断的详细分子机制仍然是未知的。在这里，我们描述了SPAS-1以浓度依赖的方式形成稳定的六聚体，SPAS-1的ATPase活性受到微管的极大刺激。此外，SPAS-1的MTBD（微管结合域）对于与微管结合至关重要。综合这些结果，我们认为SPAS-1的MTBD在SPAS-1富集到微管中起着关键作用，在该微管中，SPAS-1被浓缩并能够形成稳定的六聚体，随后刺激其ATPase活性。另一方面，我们的突变分析表明，孔区域中保守的芳香族和碱性氨基酸残基对于微管切割非常重要。我们还检测到微酸性蛋白的微酸性C末端多肽与SPAS-1的直接相互作用。因此，我们提出中心孔残基对于识别底物很重要。

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