Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Xi'an 710119, China.
Biomater Sci. 2018 Mar 26;6(4):836-841. doi: 10.1039/c8bm00066b.
Amyloid formation of proteins is not only relevant for neurodegenerative diseases, but has recently emerged as a groundbreaking approach in materials science and biotechnology. However, amyloid aggregation of proteins in vitro generally requires a long incubation time under extremely harsh conditions, and the understanding of the structural motif to determine amyloid assembly is extremely limited. Herein we reveal that the integration of three important building blocks in typical globular proteins is crucial for superfast protein amyloid-like assembly including the segment required for high fibrillation propensity, abundant α-helix structures and intramolecular S-S bonds to lock the α-helix. With the reduction of the S-S bond by tris(2-carboxyethyl)phosphine (TCEP), the α-helix was rapidly unlocked from the protein chain, and the resultant unfolded monomer underwent a fast transition to β-sheet-rich amyloid oligomers and protofibrils in minutes, which further assembled into a macroscopic nanofilm at the air/water interface and microparticles in bulk solution, respectively.
蛋白质的淀粉样蛋白形成不仅与神经退行性疾病有关，而且最近在材料科学和生物技术领域也出现了突破性的方法。然而，体外蛋白质的淀粉样聚集通常需要在极其苛刻的条件下长时间孵育，并且对决定淀粉样组装的结构基序的理解非常有限。在此，我们揭示了典型球状蛋白中三个重要结构单元的整合对于超快的蛋白质类淀粉样组装至关重要，包括高纤维化倾向所需的片段、丰富的α-螺旋结构和分子内 S-S 键以锁定α-螺旋。通过三(2-羧乙基)膦（TCEP）还原 S-S 键，α-螺旋迅速从蛋白质链中解锁，所得无规卷曲的单体在几分钟内快速转变为富含β-折叠的淀粉样寡聚物和原纤维，进一步在空气/水界面组装成宏观纳米薄膜，在本体溶液中组装成微颗粒。
