Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
B21-High Throughput SAXS	Synthetic toxic Aß 1–42 oligomers can assemble in different morphologies Claude Bobo , Stéphane Chaignepain , Sarah Henry , Hélène Vignaud , Alfred Améadan , Christelle Marchal , Enora Prado , James Doutch , Jean-Marie Schmitter , Corinne Nardin , Sophie Lecomte , Christophe Cullin Biochimica Et Biophysica Acta (bba) - General Subjects DOI: 10.1016/j.bbagen.2017.03.001 Diamond Proposal Number(s): [151] Show Abstract ▼ Abstract: Background Alzheimer's disease is the most common neurodegenerative disease associated with aggregation of Aβ peptides. Aß toxicity is mostly related to the capacity of intermediate oligomers to disrupt membrane integrity. We previously expressed Aß1–42 in a eukaryotic cellular system and selected synthetic variants on their sole toxicity. The most toxic mutant G37C forms stable oligomers. Methods Different biophysical methods (Fluorescence spectroscopy, Cross-linking, Mass spectrometry (MS), Small Angle X-Ray Scattering (SAXS), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Calcein leakage) were used. Results The oligomers are mostly populated by a 14 mers resulting from the packing of homodimers. These homodimers come from the formation of a disulfide bridge between two monomers. This link stabilizes the multimers and prevents the assembly into amyloid fibrils. These oligomers affect the membrane integrity. The reduction of disulfide bonds leads to a rearrangement and redirects assembly of Aß amyloid fibrils. Conclusion The toxic synthetic AßG37C mutant can assemble into an amyloid of unusual morphology through the formation of anti-parallel β-sheets. This pathway involves the formation of oligomers resulting from the arrangement of Aß dimers linked by covalent di-sulfide link, being these oligomers harmful for the membranes. General Significance The capacity to produce large amount of stable oligomers without additional detergents or extrinsic cross-linkers allow further structural and biophysical studies to understand their capacity to assemble and disrupt the membranes, a key event in Alzheimer's disease.	Mar 2017

Instruments / Technical Area

Publication Details

Published

Actions

B21-High Throughput SAXS

Synthetic toxic Aß 1–42 oligomers can assemble in different morphologies