Defining the Landscape of the Pauling-Corey Rippled Sheet: An Orphaned Motif Finding New Homes.
Defining the Landscape of the Pauling-Corey Rippled Sheet: An Orphaned Motif Finding New Homes.
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DOI：
10.1021/acs.accounts.1c00084
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发表时间：
2021-05-18
影响因子：
18.3
通讯作者：
Nilsson BL
中科院分区：
文献类型：
--
作者：
Raskatov JA;Schneider JP;Nilsson BL
当肽与它们的镜像以等摩尔比混合时，可以形成二维周期性结构折叠，其中延伸的肽链以交替的手性排列。由此产生的地形类，称为波纹β层，是鲍林和科里在1953年提出的理论概念。与那个时候发现的其他基本蛋白质结构基序（包括α-螺旋和折叠β-折叠）不同，它花了几十年的时间才获得支持波纹β-折叠基序的结论性实验数据。在过去十年中，通过我们三个实验室的共同努力，提供了许多关键的实验证据。专注于开发新的自组装水凝胶材料的研究已经表明，某些两亲性肽形成原纤维和水凝胶网络，当由外消旋肽混合物制成时，与纯对映异构体相比，这些原纤维和水凝胶网络更刚性并且具有更高的热力学稳定性。对由l-和d-两亲肽的混合物组成的组装体的相关询问证实，所得原纤维由与波纹β-折叠一致的交替l/d肽组成。还证明镜像淀粉样蛋白β（Aβ）可作为分子伴侣促进天然Aβ对映体的寡聚体向原纤维转化，发现这可降低Aβ对不同神经元细胞模型的神经毒性。通过结合实验和理论的跨学科方法，我们的三个实验室已经证明了在肽对映异构体混合时产生的独特的生物物理，生物化学和生物学特性，这是由于波纹β-折叠形成的结果。在本报告中，我们概述了波纹β折叠的早期历史，并提供了相对于褶皱β折叠的这种基序的详细结构描述/定义。然后，我们总结了通过我们三个实验室的独立努力在三组独特的聚合镜像肽对上获得的关键发现，并使用这些结果来描绘波纹β折叠结构基序的景观，以启发未来的研究。描述了有利于波纹β-折叠组装的肽序列参数，沿着伴随的动力学和热力学性质，以及组装体的产生的物理性质。发展账户最后简要概述了这一新生领域尚未解决的一些关键挑战。这种独特的超分子基序在材料设计和生物医学研究领域具有很大的应用潜力。我们希望这个帐户将刺激急需的讨论这个迷人的结构类，最终产生一个完全定量的，合理的框架，在未来的分子工程的波纹β-折叠。
When peptides are mixed with their mirror images in an equimolar ratio, two-dimensional periodic structural folds can form, in which extended peptide strands are arrayed with alternating chirality. The resultant topography class, termed the rippled β-sheet, was introduced as a theoretical concept by Pauling and Corey in 1953. Unlike other fundamental protein structural motifs identified around that time, including the α-helix and the pleated β-sheet, it took several decades before conclusive experimental data supporting the proposed rippled β-sheet motif were gained. Much of the key experimental evidence was provided over the course of the past decade through the concurrent efforts of our three laboratories. Studies that focused on developing new self-assembling hydrogel materials have shown that certain amphiphilic peptides form fibrils and hydrogel networks that are more rigid and have a higher thermodynamic stability when made from racemic peptide mixtures as opposed to pure enantiomers. Related interrogation of assemblies composed of mixtures of l- and d-amphiphilic peptides confirmed that the resulting fibrils were composed of alternating l/d peptides consistent with rippled β-sheets. It was also demonstrated that mirror-image amyloid beta (Aβ) could act as a molecular chaperone to promote oligomer-to-fibril conversion of the natural Aβ enantiomer, which was found to reduce Aβ neurotoxicity against different neuronal cell models. With a cross-disciplinary approach that combines experiment and theory, our three laboratories have demonstrated the unique biophysical, biochemical, and biological properties that arise upon mixing of peptide enantiomers, in consequence of rippled β-sheet formation. In this Account, we give an overview of the early history of the rippled β-sheet and provide a detailed structural description/definition of this motif relative to the pleated β-sheet. We then summarize the key findings, obtained on three unique sets of aggregating mirror-image peptide pairs through independent efforts of our three laboratories, and use these results to delineate the landscape of the rippled β-sheet structural motif to inspire future studies. Peptide sequence parameters that favor rippled β-sheet assembly are described, along with the accompanying kinetic and thermodynamic properties, as well as the resulting emergent physical properties of the assemblies. The Account then concludes with a brief overview of some key unresolved challenges in this nascent field. There is much potential for future applications of this unique supramolecular motif in the realm of materials design and biomedical research. We hope this Account will stimulate much-needed discussion of this fascinating structural class to eventually produce a fully quantitative, rational framework for the molecular engineering of rippled β-sheets in the future.
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影响因子：
14
作者：
Branco, Monica C.;Pochan, Darrin J.;Wagner, Norman J.;Schneider, Joel P.
通讯作者：
Schneider, Joel P.
影响因子：
9.8
作者：
Collins SR;Douglass A;Vale RD;Weissman JS
通讯作者：
Weissman JS
DOI：
10.1126/science.aao2825
发表时间：
2017-10-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gremer L;Schölzel D;Schenk C;Reinartz E;Labahn J;Ravelli RBG;Tusche M;Lopez-Iglesias C;Hoyer W;Heise H;Willbold D;Schröder GF
通讯作者：
Schröder GF
影响因子：
4.8
作者：
Chalifour, RJ;McLaughlin, RW;Gervais, F
通讯作者：
Gervais, F
DOI：
10.1073/pnas.0701980104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Haines-Butterick, Lisa;Rajagopal, Karthikan;Schneider, Joel P.
通讯作者：
Schneider, Joel P.