Wide diversity in structure and expression profiles among members of the Caenorhabditis elegans globin protein family.
Wide diversity in structure and expression profiles among members of the Caenorhabditis elegans globin protein family.
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秀丽隐杆线虫珠蛋白家族成员的结构和表达谱存在广泛多样性。
DOI：
10.1186/1471-2164-8-356
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发表时间：
2007-10-04
期刊：
影响因子：
4.4
通讯作者：
Vanfleteren, Jacques R.
中科院分区：
文献类型：
--
作者：
Hoogewijs, David;Geuens, Eva;Dewilde, Sylvia;Vierstraete, Andy;Moens, Luc;Vinogradov, Serge;Vanfleteren, Jacques R.
高通量基因组测序设施和强大的高性能生物信息学工具的出现凸显了珠蛋白在生命的三个王国中出人意料的广泛出现。对秀丽隐杆线虫基因组的计算机分析确定了 33 个假定的珠蛋白基因。为什么这种微小的动物可能需要如此多的球蛋白仍然是个谜。为了了解这种复杂性，我们对线虫球蛋白家族进行了结构和功能分析。所有 33 个秀丽隐杆线虫假定的珠蛋白基因均被转录。翻译的序列具有单域真正珠蛋白的基本特征，或者它们包含作为较大蛋白质一部分的独特珠蛋白域。所有珠蛋白结构域都可以排列以适合珠蛋白折叠，但内部螺旋间、N 端和 C 端延伸以及各种氨基酸取代在秀丽隐杆线虫的珠蛋白中产生了很多结构多样性。同样，编码基因缺乏内含子插入定位的保守模式。我们分析了生命周期进展过程中球蛋白的表达谱，发现在野生型 dauers 和 daf-2(e1370)/胰岛素受体突变体成年动物中，不同的球蛋白子集被诱导或抑制，尽管这些动物具有一些共同的生理特征，包括对高温、氧化应激和缺氧死亡的抵抗力。一些珠蛋白基因在缺氧后上调，我们发现 HIF-1 和 DAF-2 都是这种反应所必需的。我们的数据表明，DAF-2 调节转录因子 DAF-16/FOXO 在缺氧条件下正向调节 hif-1 转录，但反对 HIF-1 响应珠蛋白基因本身的表达。相比之下，线虫的典型珠蛋白 ZK637.13 对缺氧没有反应。 DAF-2 信号传导的减少会导致该珠蛋白的转录增强，而这种效果需要 DAF-16。我们发现所有 33 种假定的球蛋白均表达，尽管水平较低或非常低，这可能表明细胞特异性表达。它们在基因结构和氨基酸序列上表现出广泛的多样性，表明它们具有悠久的进化历史。十个珠蛋白以依赖 HIF-1 和 DAF-16 的相互作用方式对缺氧做出反应。珠蛋白 ZK637.13 对缺氧没有反应，并受 Ins/IGF 途径调节，仅表明该珠蛋白可能有助于生命维持程序。
The emergence of high throughput genome sequencing facilities and powerful high performance bioinformatic tools has highlighted hitherto unexpected wide occurrence of globins in the three kingdoms of life. In silico analysis of the genome of C. elegans identified 33 putative globin genes. It remains a mystery why this tiny animal might need so many globins. As an inroad to understanding this complexity we initiated a structural and functional analysis of the globin family in C. elegans. All 33 C. elegans putative globin genes are transcribed. The translated sequences have the essential signatures of single domain bona fide globins, or they contain a distinct globin domain that is part of a larger protein. All globin domains can be aligned so as to fit the globin fold, but internal interhelical and N- and C-terminal extensions and a variety of amino acid substitutions generate much structural diversity among the globins of C. elegans. Likewise, the encoding genes lack a conserved pattern of intron insertion positioning. We analyze the expression profiles of the globins during the progression of the life cycle, and we find that distinct subsets of globins are induced, or repressed, in wild-type dauers and in daf-2(e1370)/insulin-receptor mutant adults, although these animals share several physiological features including resistance to elevated temperature, oxidative stress and hypoxic death. Several globin genes are upregulated following oxygen deprivation and we find that HIF-1 and DAF-2 each are required for this response. Our data indicate that the DAF-2 regulated transcription factor DAF-16/FOXO positively modulates hif-1 transcription under anoxia but opposes expression of the HIF-1 responsive globin genes itself. In contrast, the canonical globin of C. elegans, ZK637.13, is not responsive to anoxia. Reduced DAF-2 signaling leads to enhanced transcription of this globin and DAF-16 is required for this effect. We found that all 33 putative globins are expressed, albeit at low or very low levels, perhaps indicating cell-specific expression. They show wide diversity in gene structure and amino acid sequence, suggesting a long evolutionary history. Ten globins are responsive to oxygen deprivation in an interacting HIF-1 and DAF-16 dependent manner. Globin ZK637.13 is not responsive to oxygen deprivation and regulated by the Ins/IGF pathway only suggesting that this globin may contribute to the life maintenance program.
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1.5
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