Anand Bibin G, Prajapati Kailash P, Shekhawat Dolat S, Kar Karunakar
Biophysical and Biomaterials Research Laboratory, Room 310, School of Life Sciences , Jawaharlal Nehru University , New Delhi 110067 , India.
Biochemistry. 2018 Sep 4;57(35):5202-5209. doi: 10.1021/acs.biochem.8b00472. Epub 2018 Aug 20.
Here, we show that aromatic amino acid tyrosine, under a physiologically mimicking condition, readily forms amyloid-like entities that can effectively drive aggregation of different globular proteins and aromatic residues. Tyrosine self-assembly resulted in the formation of cross-β rich regular fibrils as well as spheroidal oligomers. Computational data suggest intermolecular interaction between specifically oriented tyrosine molecules mediated through π-π stacking and H-bonding interactions, mimicking a cross-β-like architecture. Both individual protein samples and mixed protein samples underwent aggregation in the presence of tyrosine fibrils, confirming the occurrence of amyloid cross-seeding. The surface of the tyrosine's amyloid like entities was predicted to trap native protein structures, preferably through hydrophobic and electrostatic interactions initiating an aggregation event. Because tyrosine is a precursor to vital neuromodulators, the inherent cross-seeding potential of the tyrosine fibrils may have direct relevance to amyloid-linked pathologies.
在此，我们表明，在生理模拟条件下，芳香族氨基酸酪氨酸很容易形成类淀粉样实体，这些实体能够有效地驱动不同球状蛋白和芳香族残基的聚集。酪氨酸自组装导致形成富含交叉β结构的规则纤维以及球状寡聚体。计算数据表明，通过π-π堆积和氢键相互作用介导的特定取向的酪氨酸分子之间存在分子间相互作用，模拟了类似交叉β的结构。无论是单个蛋白质样品还是混合蛋白质样品，在酪氨酸纤维存在的情况下都会发生聚集，证实了淀粉样交叉播种的发生。酪氨酸类淀粉样实体的表面预计会捕获天然蛋白质结构，最好是通过疏水和静电相互作用引发聚集事件。由于酪氨酸是重要神经调节剂的前体，酪氨酸纤维固有的交叉播种潜力可能与淀粉样蛋白相关的病理学直接相关。
