Bhowmik, Debanjan ; Mote, Kaustubh R. ; MacLaughlin, Christina M. ; Biswas, Nupur ; Chandra, Bappaditya ; Basu, Jaydeep K. ; Walker, Gilbert C. ; Madhu, Perunthiruthy K. ; Maiti, Sudipta (2015) Cell-Membrane-Mimicking Lipid-Coated Nanoparticles Confer Raman Enhancement to Membrane Proteins and Reveal Membrane-Attached Amyloid-β Conformation ACS Nano, 9 (9). pp. 9070-9077. ISSN 1936-0851
Full text not available from this repository.
Official URL: http://doi.org/10.1021/acsnano.5b03175
Related URL: http://dx.doi.org/10.1021/acsnano.5b03175
Abstract
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-β40 (Aβ40), 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 β-turn, flanked by two β-sheet regions. We use solid-state NMR data to confirm the presence of the β-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 Aβ fibrils. Significantly, this allows a “porin” like β-barrel structure, providing a structural basis for proposed mechanisms of Aβ oligomer toxicity.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to American Chemical Society. |
Keywords: | Amyloid Beta Peptide; Oligomers; Surface Enhanced Raman Spectroscopy; Membrane Protein Structures; Solid-state Nmr; Lipid Sers; Lipid-coated Nanoparticles. |
ID Code: | 116074 |
Deposited On: | 22 Mar 2021 07:00 |
Last Modified: | 22 Mar 2021 07:00 |
Repository Staff Only: item control page