Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid.
Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid.
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Dock n roll：将受丝启发的多肽折叠成淀粉样蛋白样β螺线管。
DOI：
10.1039/c6sm00169f
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发表时间：
2016
期刊：
影响因子：
3.4
通讯作者：
Hall,CarolK
中科院分区：
文献类型：
--
作者：
Zhao,Binwu;CohenStuart,MartienA;Hall,CarolK
含有基序（（GA）mGX）n的多肽存在于丝中，并且具有强烈的自组装倾向。例如，含有（GAGAGAGX）n的多肽，其中X = G或H，已被观察到形成细丝;类似的序列，但X = Q已被用于设计人工病毒的外壳蛋白（衣壳）。已经提出（GAGAGAGX）m细丝的结构是β卷结构中的肽堆叠，其中疏水侧链指向外（疏水壳）。然而，另一种可能的构型，β卷或β螺线管结构，其具有埋在内部的疏水侧链（疏水核），被忽略了。我们进行基态分析，以及原子水平的分子动力学模拟，无论是在单分子和双分子堆栈的丝绸启发序列（GAGAGAGQ）10，以决定是否疏水核或疏水壳配置是最稳定的。我们发现，两个疏水核分子的堆叠在能量上比两个疏水壳分子的堆叠更有利。最初处于完美β卷结构中的壳分子倾向于旋转其链，破坏面内氢键并形成面外氢键，而核心分子则保持在β卷结构中。疏水性壳结构具有II′ β转角，而核构型具有II β转角;只有后者的二级结构与类似序列（GA）的固态NMR实验吻合良好15。我们还观察到，核堆具有较高数量的分子内氢键和较高数量的氢键之间的堆栈和水比壳堆栈。因此，我们得出结论，疏水核构型是最可能的结构。在堆叠状态下，每个肽具有比单个折叠分子更多的分子内氢键，这表明堆叠提供了分子达到折叠状态所需的额外稳定性。
Polypeptides containing the motif ((GA)mGX)n occur in silk and have a strong tendency to self-assemble. For example, polypeptides containing (GAGAGAGX)n, where X = G or H have been observed to form filaments; similar sequences but with X = Q have been used in the design of coat proteins (capsids) for artificial viruses. The structure of the (GAGAGAGX)m filaments has been proposed to be a stack of peptides in a β roll structure with the hydrophobic side chains pointing outwards (hydrophobic shell). Another possible configuration, a β roll or β solenoid structure which has its hydrophobic side chains buried inside (hydrophobic core) was, however, overlooked. We perform ground state analysis as well as atomic-level molecular dynamics simulations, both on single molecules and on two-molecule stacks of the silk-inspired sequence (GAGAGAGQ)10, to decide whether the hydrophobic core or the hydrophobic shell configuration is the most stable one. We find that a stack of two hydrophobic core molecules is energetically more favorable than a stack of two hydrophobic shell molecules. A shell molecule initially placed in a perfect β roll structure tends to rotate its strands, breaking in-plane hydrogen bonds and forming out-of-plane hydrogen bonds, while a core molecule stays in the β roll structure. The hydrophobic shell structure has type II′ β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence (GA)15. We also observe that the core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack. Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for molecules to reach the folded state.