Molecular Medicine, The Hospital for Sick Children, Toronto, Canada.
Department of Biochemistry, University of Toronto, Toronto, Canada.
Elife. 2017 Nov 9;6:e26526. doi: 10.7554/eLife.26526.
The protein elastin imparts extensibility, elastic recoil, and resilience to tissues including arterial walls, skin, lung alveoli, and the uterus. Elastin and elastin-like peptides are hydrophobic, disordered, and undergo liquid-liquid phase separation upon self-assembly. Despite extensive study, the structure of elastin remains controversial. We use molecular dynamics simulations on a massive scale to elucidate the structural ensemble of aggregated elastin-like peptides. Consistent with the entropic nature of elastic recoil, the aggregated state is stabilized by the hydrophobic effect. However, self-assembly does not entail formation of a hydrophobic core. The polypeptide backbone forms transient, sparse hydrogen-bonded turns and remains significantly hydrated even as self-assembly triples the extent of non-polar side chain contacts. Individual chains in the assembly approach a maximally-disordered, melt-like state which may be called the liquid state of proteins. These findings resolve long-standing controversies regarding elastin structure and function and afford insight into the phase separation of disordered proteins.
弹性蛋白赋予组织（包括动脉壁、皮肤、肺肺泡和子宫）伸展性、弹性回弹和弹性恢复能力。弹性蛋白和弹性蛋白样肽是疏水性的、无规则的，在自组装时会发生液-液相分离。尽管已经进行了广泛的研究，但弹性蛋白的结构仍然存在争议。我们使用大规模的分子动力学模拟来阐明聚集的弹性蛋白样肽的结构组合。与弹性回弹的熵性质一致，聚集态通过疏水作用稳定。然而，自组装并不需要形成疏水性核心。多肽主链形成短暂的、稀疏的氢键转弯，并且即使自组装将非极性侧链接触的程度增加了三倍，仍然保持显著的水合状态。组装中的各个链接近一种最大无序、类似熔体的状态，这种状态可能被称为蛋白质的液体状态。这些发现解决了关于弹性蛋白结构和功能的长期争议，并为无序蛋白质的相分离提供了深入的了解。
