7O1Q

Amyloid beta oligomer displayed on the alpha hemolysin scaffold

Summary for 7O1Q

• Entry DOI: 10.2210/pdb7o1q/pdb
• EMDB information: 12696
• Descriptor: Alpha-hemolysin hybridized Abeta (1 entity in total)
• Functional Keywords: amyloid beta oligomer, alpha hemolysin, alzheimer's disease, toxin
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 7
• Total formula weight: 234214.89

Authors

Wu, J.,Blum, T.B.,Farrell, D.P.,DiMaio, F.,Abrahams, J.P.,Luo, J. (deposition date: 2021-03-30, release date: 2021-04-14, Last modification date: 2024-07-10)

Primary citation

Wu, J.,Blum, T.B.,Farrell, D.P.,DiMaio, F.,Abrahams, J.P.,Luo, J.
Cryo-electron Microscopy Imaging of Alzheimer's Amyloid-beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold.
Angew.Chem.Int.Ed.Engl., 60:18680-18687, 2021

PubMed Abstract: Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure of these pores remains to be characterized. We studied a functional Aβ42-pore equivalent, created by fusing Aβ42 to the oligomerizing, soluble domain of the α-hemolysin (αHL) toxin. Our data reveal Aβ42-αHL oligomers to share major structural, functional, and biological properties with wild-type Aβ42-pores. Single-particle cryo-EM analysis of Aβ42-αHL oligomers (with an overall 3.3 Å resolution) reveals the Aβ42-pore region to be intrinsically flexible. The Aβ42-αHL oligomers will allow many of the features of the wild-type amyloid oligomers to be studied that cannot be otherwise, and may be a highly specific antigen for the development of immuno-base diagnostics and therapies.

PubMed: 34042235
DOI: 10.1002/anie.202104497

Experimental method

ELECTRON MICROSCOPY (3.4 Å)