Nanoscale Infrared Spectroscopy Identifies Parallel to Antiparallel β-Sheet Transformation of Aβ Fibrils.
Nanoscale Infrared Spectroscopy Identifies Parallel to Antiparallel β-Sheet Transformation of Aβ Fibrils.
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DOI：
10.1021/acs.jpclett.2c02998
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发表时间：
2022-11-17
影响因子：
5.7
通讯作者：
Ghosh, Ayanjeet
中科院分区：
文献类型：
--
作者：
Banerjee, Siddhartha;Baghel, Divya;Iqbal, Md Hasan Ul;Ghosh, Ayanjeet
淀粉样β蛋白(Aβ)的自发聚集导致低聚体的形成并最终形成纤维，已被认为是阿尔茨海默病的关键病理标志。用核磁共振、X射线结晶学和红外光谱等常规结构生物学技术对晚期聚集体的结构进行了深入的研究，但由于其暂时性，对早期聚集体的结构知之甚少。因此，淀粉样蛋白聚集体从早期的低聚物到成熟的纤维的结构进化仍然不完全清楚。在这里，我们应用原子力显微镜-红外纳米光谱来研究Aβ16-22的聚集，它横跨淀粉样β多肽的淀粉样形成核心。我们的结果表明，Aβ16-22通过无序的和可能的螺旋中间纤维结构，参与了从平行β片寡聚体到反平行纤维的结构转变，与已知的全长Aβ的聚集途径相反。
Spontaneous aggregation of amyloid beta (Aβ) proteins leading to the formation of oligomers and eventually into fibrils has been identified as a key pathological signature of Alzheimer’s disease. Structure of late-stage aggregates have been studied in depth by conventional structural biology techniques including Nuclear Magnetic Resonance, X-ray crystallography and Infrared Spectroscopy; however, the structure of early-stage aggregates is less known due to their transient nature. As a result, the structural evolution of amyloid aggregates from its early oligomers to mature fibril is still not fully understood. Here we have applied AFM-IR nanospectroscopy to investigate the aggregation of Aβ 16-22, which spans the amyloidogenic core of the amyloid beta peptide. Our results demonstrate that Aβ 16-22 involves a structural transition from oligomers with parallel beta sheets to antiparallel fibrils through disordered and possibly helical intermediate fibril structures, contrary to the known aggregation pathway of full-length Aβ.
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影响因子：
15
作者：
Wickramasinghe, Ayesha;Xiao, Yiling;Kobayashi, Naohiro;Wang, Songlin;Scherpelz, Kathryn P.;Yamazaki, Toshio;Meredith, Stephen C.;Ishii, Yoshitaka
通讯作者：
Ishii, Yoshitaka
DOI：
10.1073/pnas.1911153117
发表时间：
2020-05-12
影响因子：
11.1
作者：
Jia, Zhiguang;Schmit, Jeremy D.;Chen, Jianhan
通讯作者：
Chen, Jianhan
影响因子：
16.2
作者：
Tycko, Robert
通讯作者：
Tycko, Robert
影响因子：
15
作者：
Liang, Chen;Ni, Rong;Lynn, David G.
通讯作者：
Lynn, David G.
DOI：
10.1073/pnas.230315097
发表时间：
2000-11-21
影响因子：
11.1
作者：
Antzutkin, ON;Balbach, JJ;Tycko, R
通讯作者：
Tycko, R