Key Laboratory of Colloid and Interface Chemistry of the Ministry of, Education, and School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, P. R. China.
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, 8000, Denmark.
Chemistry. 2020 Aug 3;26(43):9449-9453. doi: 10.1002/chem.201905715. Epub 2020 Jul 20.
HIV transactivator of transcription (Tat) protein could interact with amyloid β (Aβ) peptide which cause the growth of Aβ plaques in the brain and result in Alzheimer's disease in HIV-infected patients. Herein, we employ high-resolution atomic force microscopy and quantitative nanomechanical mapping to investigate the effects of Tat protein in Aβ peptide aggregation. Our results demonstrate that the Tat protein could bind to the Aβ fibril surfaces and result in the formation of Tat-Aβ multifibrillar structures. The resultant Tat-Aβ multifibrillar aggregates represent an increase in stiffness compared with Aβ fibrils due to the increase in β-sheet formation. The identification and characterization of the Tat-Aβ intermediate aggregates is important to understanding the interactions between Tat protein and Aβ peptide, and the development of novel therapeutic strategy for Alzheimer's disease-like disorder in HIV infected individuals.
HIV 转录激活蛋白（Tat）可以与淀粉样β（Aβ）肽相互作用，导致大脑中 Aβ斑块的生长，并导致感染 HIV 的患者发生阿尔茨海默病。在此，我们采用高分辨率原子力显微镜和定量纳米力学映射来研究 Tat 蛋白对 Aβ肽聚集的影响。研究结果表明，Tat 蛋白可以与 Aβ 原纤维表面结合，形成 Tat-Aβ 多原纤维结构。由于β-折叠形成增加，与 Aβ 原纤维相比，形成的 Tat-Aβ 多原纤维聚集物的刚性增加。鉴定和表征 Tat-Aβ 中间聚集物对于理解 Tat 蛋白和 Aβ 肽之间的相互作用以及开发针对感染 HIV 的个体中类似阿尔茨海默病障碍的新型治疗策略非常重要。
