A conserved spider silk domain acts as a molecular switch that controls fibre assembly
A conserved spider silk domain acts as a molecular switch that controls fibre assembly
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DOI：
10.1038/nature08936
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发表时间：
2010-05-13
期刊：
影响因子：
64.8
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
--
作者：
Hagn, Franz;Eisoldt, Lukas;Kessler, Horst
种类繁多的蛋白质能够形成纤维状结构(1)，特别是在高蛋白质浓度下。因此，令人惊讶的是，蜘蛛丝蛋白可以在高浓度下以可溶性形式储存，并根据需要转化为极其稳定的纤维（2,3）。丝绸蛋白让人联想到两亲性嵌段共聚物，含有富含聚丙氨酸和甘氨酸的极性元素，形成一个重复核心，两侧是高度保守的非重复氨基末端（4,5）和羧基末端(6)结构域。n端结构域包括一个分泌信号，但进一步的功能仍未确定。c端结构域涉及控制溶解度和纤维形成(7)，这是由离子组成的变化（8,9）和已知的机械刺激引起的，这些刺激可以对齐重复序列元素并促进β -片的形成（10-14）。然而，尽管有最近的结构数据（15），人们对这种显著行为的分子细节知之甚少。本文提出了蜘蛛拖丝蛋白c端结构域的解结构，并提供证据表明该结构域的结构状态对于控制丝蛋白在储存和组装形式之间的转换至关重要。此外，c端结构域还在蜘蛛丝蛋白主链中由重复元素形成的二级结构特征的排列中发挥作用，这对于纤维的机械性能是重要的。
A huge variety of proteins are able to form fibrillar structures(1), especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand(2,3). Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal(4,5) and carboxy-terminal(6) domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation(7) initiated by changes in ionic composition(8,9) and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation(10-14). However, despite recent structural data(15), little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.