Pore-forming proteins share structural and functional homology with amyloid oligomers

Yuji Yoshiike, Rakez Kayed, Saskia C. Milton, Akihiko Takashima, Charles G. Glabe

    Research output: Contribution to journalArticlepeer-review

    58 Scopus citations


    Degenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases are believed to be causally related to the accumulation of amyloid oligomers that exhibit a common structure and may be toxic by a common mechanism involving permeabilization of membranes. We discovered that amyloid oligomers and the pore-forming bacterial toxin, α-hemolysin (αHL), as well as human perforin from cytotoxic T lymphocytes, share a structural and functional homology at the level of their common reactivity with a conformation-dependent antibody that is specific for amyloid oligomers, A11. The αHL oligomeric pores and partially folded αHL protomer, but not the monomer αHL precursor reacts with A11 antibody. A11 antibody inhibits the hemolytic activity of αHL, indicating that the structural homology is functionally significant. Perforin oligomers were also recognized by A11. Amyloidogenic properties of αHL and perforin were confirmed spectroscopically and morphologically. These results indicate that pore forming proteins (PFP) and amyloid oligomers share structural homology and suggest that PFPs and amyloid oligomers share the same mechanism of membrane permeabilization.

    Original languageEnglish (US)
    Pages (from-to)270-275
    Number of pages6
    JournalNeuroMolecular Medicine
    Issue number3
    StatePublished - Sep 2007


    • Alzheimer's disease
    • Amyloid-β
    • Hemolysis
    • Perforin
    • Pore-forming protein
    • Toxicity
    • α-Hemolysin

    ASJC Scopus subject areas

    • Molecular Medicine
    • Neurology
    • Cellular and Molecular Neuroscience


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