Dishevelled C-terminus: prolyl and histidinyl motifs.

Dishevelled C-terminus: prolyl and histidinyl motifs.
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蓬乱的 C 末端:脯氨酰和组氨酰基序。

DOI:
10.1111/j.1748-1716.2011.02291.x
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发表时间:
2012-01
期刊:
Acta physiologica (Oxford, England)
影响因子:
--
通讯作者:
Malbon CC
Malbon CC
中科院分区:
其他
文献类型:
--
作者:
Wang HY;Malbon CC

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凌乱的磷蛋白支架是Wnt信号和信号体的重要组成部分,信号体构成了经常在荧光显微镜下观察到的组装蛋白的超分子“点状”。DEP结构域之外的C-末端区域显示出独特而有趣的特征,本文通过仔细分析一级结构来利用这一特征。人类杂乱-1、-2、-3和苍蝇杂乱(Dsh)序列被下载并在电子计算机中被询问。FoldIndex®显示Disheveled-3的C末端具有丰富的有序结构。它显示的初级序列是唯一的,在重要方面与脊椎动物的亚型以及苍蝇的Dsh存在差异。该地区是两亲性的,脯氨酸含量很高,并含有多聚脯氨酸。Disheveled-3显示了Pro含量为40%的某些区域。多聚脯氨酸序列(2-4个残基)可能构成与其他杂乱的异构体相互作用的重要部位。值得注意的是几个组氨酸-单一氨基酸重复。Dvl3的637,638/647,648重复对于WNT非规范信号是必要的,但不是规范信号。突变实验表明,C-末端序列对于形成荧光显微镜下可见的点状突起是必不可少的。这些基于Dvl3的信号体是非常大的(25-35 mW)超分子复合体,对Wnt刺激表现出动态重组。杂乱的C-末端具有丰富的结构和独特的基序,值得用现代分子工具进行详细的分析。
The phosphoprotein scaffold Dishevelled is an essential component of both Wnt signaling and of the signalsome that constitutes the supermolecular “punctae” of assembled proteins often observed in fluorescence microscopy. The C-terminal region beyond the DEP domain displays unique and interesting character, exploited herein by careful analysis of the primary structure. Human Dishevelled-1, -2, -3 and fly Dishevelled (Dsh) sequences were downloaded and interrogated in silico. The C-terminus of Dishevelled-3 is revealed by FoldIndex® to be rich in ordered structure. It displays primary sequence that is unique and divergent in important ways from vertebrate isoforms as well as from the fly Dsh. The region is amphipathic, high in prolyl content, and harbors polyprolines. Dishevelled-3 displays some regions where the proline content is >40%. Polyprolyl sequences (2–4 residues) likely constitute important sites of interaction with other Dishevelled isoforms. Several histidine-single amino acid repeats are notable. The 637,638/647,648 repeats of Dvl3 are essential for Wnt non-canonical, but not canonical signaling. Mutagenesis reveals that the C-terminal sequence is essential for the formation of punctae, made visible by fluorescence microscopy. These Dvl3-based signalsomes are very large (25–35 MDa MW), supermolecular complexes that display dynamic reorganization in response to Wnt stimulation. Dishevelled-3 C-terminus is rich in structure and unique motifs, worthy of detailed analysis with modern molecular tools.
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