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Publication Abstract from PubMed

Amyloid-beta peptide (Abeta) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Abeta oligomers permeabilize cellular membranes, presumably through a pore formation mechanism. Due to their structural and stoichiometric heterogeneity, the structure of these pores remains to be characterized. We studied a functional Abeta42-pore equivalent, created by fusing Abeta42 to the oligomerizing, soluble domain of the alpha-hemolysin (alphaHL) toxin. Our data reveal Abeta42-alphaHL oligomers to share major structural, functional and biological properties with wild-type Abeta42-pores. Single-particle cryo-EM analysis of Abeta42-alphaHL oligomers (with an overall resolution of 3.3 A) reveals the Abeta42-pore region to be intrinsically flexible. We anticipate that the Abeta42-alphaHL oligomers will allow studying many of the features of the wild type amyloid oligomers that cannot be studied otherwise, and may represent a highly specific antigen for the development of immuno-base diagnostics and therapies.

Cryo-electron microscopy imaging of Alzheimer's amyloid-beta 42 oligomer displayed on a functionally and structurally relevant scaffold.,Wu J, Blum TB, Farrell DP, DiMaio F, Abrahams JP, Luo J Angew Chem Int Ed Engl. 2021 May 27. doi: 10.1002/anie.202104497. PMID:34042235^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.