Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.
Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.
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热带素分子形状和柔韧性的微妙平衡调节动力学和分层组件。
DOI：
10.1126/sciadv.1501145
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发表时间：
2016-02
期刊：
影响因子：
13.6
通讯作者：
Weiss AS
中科院分区：
文献类型：
--
作者：
Yeo GC;Tarakanova A;Baldock C;Wise SG;Buehler MJ;Weiss AS
原弹性蛋白的局部和全局结构决定了分子动力学，并且对于有效组装成弹性蛋白是必不可少的。原弹性蛋白单体组装成弹性蛋白对于赋予血管、皮肤和肺弹性至关重要。原弹性蛋白在自组装中具有对柔性和结构的双重需求。我们探讨的结构动力学功能的相互作用，考虑分子有序和无序的二重性，并确定同样重要的功能的本地和全球结构的贡献。为了研究这些组织分层，我们通过表达在人类原弹性蛋白中普遍剪接的外显子来扰乱关键铰链区。我们发现了一个突出的纳米结构与位移的C端，并解释了分子建模，灵活的螺旋被大量的β片层取代。我们看到非典型的高阶交联和低效组装成不连续的厚弹性纤维。我们解释这种功能障碍，相关的局部和全局结构的影响与分子的组装动力学的变化。这项工作对我们理解弹性蛋白具有普遍意义，弹性蛋白在多个尺度上平衡无序区域与定义的结构模块进行功能组装。
Tropoelastin’s local and global structures dictate molecular dynamics and are essential for efficient assembly into elastin. The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule’s assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.