期刊
ACS NANO
卷 9, 期 9, 页码 9070-9077出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b03175
关键词
amyloid beta peptide; oligomers; surface enhanced Raman spectroscopy; membrane protein structures; solid-state NMR; lipid SERS; lipid-coated nanoparticles
类别
资金
- Department of Biotechnology, India [BT/53/NE/TBP/2010]
- ARCI, India [ARCI/D/FAO/Nano/K-16/Canada/11]
- Department of Science and Technology, India
- NSERC, Canada
- CSIR-SPM-SRF
Identifying the structures of membrane bound proteins is critical to understanding their function in healthy and diseased states. We introduce a surface enhanced Raman spectroscopy technique which can determine the conformation of membrane-bound proteins, at low micromolar concentrations, and also in the presence of a substantial membrane-free fraction. Unlike conventional surface enhanced Raman spectroscopy, our approach does not require immobilization of molecules, as it uses spontaneous binding of proteins to lipid bilayer-encapsulated Ag nanoparticles. We apply this technique to probe membrane-attached oligomers of Amyloid-beta(40) (A beta(40)), whose conformation is keenly sought in the context of Alzheimer's disease. Isotope-shifts in the Raman spectra help us obtain secondary structure information at the level of individual residues. Our results show the presence of a beta-turn, flanked by two beta-sheet regions. We use solid-state NMR data to confirm the presence of the beta-sheets in these regions. In the membrane-attached oligomer, we find a strongly contrasting and near-orthogonal orientation of the backbone H-bonds compared to what is found in the mature, less-toxic A beta fibrils. Significantly, this allows a porin like beta-barrel structure, providing a structural basis for proposed mechanisms of A beta oligomer toxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据