Balasco Nicole, Diaferia Carlo, Morelli Giancarlo, Vitagliano Luigi, Accardo Antonella
Institute of Biostructures and Bioimaging (IBB), CNR, Naples, Italy.
Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Naples, Italy.
Front Bioeng Biotechnol. 2021 Mar 3;9:641372. doi: 10.3389/fbioe.2021.641372. eCollection 2021.
The discovery that the polypeptide chain has a remarkable and intrinsic propensity to form amyloid-like aggregates endowed with an extraordinary stability is one of the most relevant breakthroughs of the last decades in both protein/peptide chemistry and structural biology. This observation has fundamental implications, as the formation of these assemblies is systematically associated with the insurgence of severe neurodegenerative diseases. Although the ability of proteins to form aggregates rich in cross-β structure has been highlighted by recent studies of structural biology, the determination of the underlying atomic models has required immense efforts and inventiveness. Interestingly, the progressive molecular and structural characterization of these assemblies has opened new perspectives in apparently unrelated fields. Indeed, the self-assembling through the cross-β structure has been exploited to generate innovative biomaterials endowed with promising mechanical and spectroscopic properties. Therefore, this structural motif has become the connecting these diversified research areas. In the present review, we report a chronological recapitulation, also performing a survey of the structural content of the Protein Data Bank, of the milestones achieved over the years in the characterization of cross-β assemblies involved in the insurgence of neurodegenerative diseases. A particular emphasis is given to the very recent successful elucidation of amyloid-like aggregates characterized by remarkable molecular and structural complexities. We also review the state of the art of the structural characterization of cross-β based biomaterials by highlighting the benefits of the osmosis of information between these two research areas. Finally, we underline the new promising perspectives that recent successful characterizations of disease-related amyloid-like assemblies can open in the biomaterial field.
多肽链具有形成具有非凡稳定性的淀粉样聚集体的显著内在倾向，这一发现是过去几十年蛋白质/肽化学和结构生物学领域最相关的突破之一。这一观察结果具有重要的意义，因为这些聚集体的形成与严重神经退行性疾病的发生系统性相关。尽管结构生物学的最新研究突出了蛋白质形成富含交叉β结构聚集体的能力，但确定其潜在的原子模型需要巨大的努力和创造力。有趣的是，这些聚集体的逐步分子和结构表征在明显不相关的领域开辟了新的前景。事实上，通过交叉β结构的自组装已被用于制造具有良好机械和光谱特性的创新生物材料。因此，这个结构基序已成为连接这些不同研究领域的纽带。在本综述中，我们按时间顺序进行了总结，还对蛋白质数据库的结构内容进行了调查，介绍了多年来在表征与神经退行性疾病发生相关的交叉β聚集体方面取得的里程碑式进展。我们特别强调了最近成功阐明的具有显著分子和结构复杂性的淀粉样聚集体。我们还通过强调这两个研究领域之间信息渗透的好处，回顾了基于交叉β的生物材料结构表征的现状。最后，我们强调了最近与疾病相关的淀粉样聚集体的成功表征在生物材料领域可能开启的新的有前景的前景。
