The ASCH superfamily: novel domains with a fold related to the PUA domain and a potential role in RNA metabolism
The ASCH superfamily: novel domains with a fold related to the PUA domain and a potential role in RNA metabolism
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DOI：
10.1093/bioinformatics/bti767
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发表时间：
2006-02-01
期刊：
影响因子：
5.8
通讯作者：
Aravind, L
中科院分区：
文献类型：
--
作者：
Iyer, LM;Burroughs, AM;Aravind, L
一些研究表明，转录共激活因子通常是双功能核糖核蛋白复合物，也调节前mrna加工和剪接决策。通过敏感序列搜索和结构比较，我们发现人类辅助激活蛋白ASC-1的c端结构域定义了一个新的超家族，ASC-1同源性（ASCH）结构域。大约110个氨基酸长的ASCH结构域广泛存在于所有三个生命超级王国和几种原核病毒中。我们发现ASCH超家族采用类似于PUA结构域超家族的β -桶状褶皱。利用多种证据，我们认为ASCH超家族的成员可能在与共激活、rna加工和可能的原核翻译调控相关的环境中起rna结合域的作用。ASCH结构域的结构分析揭示了与保守序列基序相关的潜在rna结合裂缝的存在，这是该超家族的特征。尽管它们的结构相似，ASCH和PUA结构域似乎占据不同的功能位，前者结构域通常以独立的形式出现在多肽中，后者结构域与多种rna修饰酶融合。
Several studies show that transcription coactivators are often bi-functional ribonucleoprotein complexes that also regulate pre-mRNA processing and splicing decisions. Using sensitive sequence profile searches and structural comparisons we show that the C-terminal domain of the human coactivator protein ASC-1 defines a novel superfamily, the ASC-1 homology (ASCH) domain. The approximately 110 amino acid long ASCH domains are widely represented in all the three superkingdoms of life and several prokaryotic viruses. We show that the ASCH superfamily adopts a beta-barrel fold similar to the PUA domain superfamily. Using multiple lines of evidence, we suggest that members of the ASCH superfamily are likely to function as RNA-binding domains in contexts related to coactivation, RNA-processing and possibly prokaryotic translation regulation. Structural analysis of ASCH domains reveals the presence of a potential RNA-binding cleft associated with a conserved sequence motif, which is characteristic of this superfamily. Despite their similar structure, the ASCH and PUA domains appear to occupy distinct functional niches, with the former domains typically occurring in a standalone form in polypeptides, and the latter domains showing fusions to a variety of RNA-modifying enzymes.