Center for Integrated Protein Science (CIPSM), Technische Universität München, 85747 Garching, Germany.
Nature. 2010 May 13;465(7295):239-42. doi: 10.1038/nature08936.
A huge variety of proteins are able to form fibrillar structures, 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. 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 and carboxy-terminal 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 initiated by changes in ionic composition and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation. However, despite recent structural data, 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.
大量的蛋白质能够形成纤维状结构，尤其是在高蛋白质浓度下。因此，令人惊讶的是，蜘蛛丝蛋白能够以高浓度的可溶性形式储存，并根据需要转化为极其稳定的纤维。丝蛋白类似于两亲性嵌段共聚物，其中包含伸展的富含丙氨酸和甘氨酸的极性元件，形成一个由高度保守的非重复的氨基末端和羧基末端结构域侧翼的重复核心。N 末端结构域包含一个分泌信号，但其他功能仍然没有被分配。C 末端结构域被认为参与控制溶解度和纤维形成，这是由离子组成和机械刺激的变化引起的，已知这些变化可以使重复序列元件对齐并促进β-折叠形成。然而，尽管有最近的结构数据，但对于这种分子细节的显著行为知之甚少。在这里，我们展示了蜘蛛拖丝丝蛋白 C 末端结构域的溶液结构，并提供了证据表明该结构域的结构状态对于丝蛋白的储存和组装形式之间的可控切换是必不可少的。此外，C 末端结构域还在蜘蛛丝蛋白骨架中重复元件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很重要的。
