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 journalArticle

48 Citations (Scopus)

Abstract

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
Volume9
Issue number3
DOIs
StatePublished - Sep 2007

Fingerprint

Porins
Hemolysin Proteins
Amyloid
Perforin
Antibodies
Bacterial Toxins
Membranes
Poisons
Huntington Disease
Protein Subunits
Cytotoxic T-Lymphocytes
Parkinson Disease
Alzheimer Disease

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

Cite this

Pore-forming proteins share structural and functional homology with amyloid oligomers. / Yoshiike, Yuji; Kayed, Rakez; Milton, Saskia C.; Takashima, Akihiko; Glabe, Charles G.

In: NeuroMolecular Medicine, Vol. 9, No. 3, 09.2007, p. 270-275.

Research output: Contribution to journalArticle

Yoshiike, Yuji ; Kayed, Rakez ; Milton, Saskia C. ; Takashima, Akihiko ; Glabe, Charles G. / Pore-forming proteins share structural and functional homology with amyloid oligomers. In: NeuroMolecular Medicine. 2007 ; Vol. 9, No. 3. pp. 270-275.
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