Title
Amyloid ion channels: A common structural link for protein-misfolding disease
Author
Arjan Quist, Ivo Doudevski, Hai Lin, Rushana Azimova, Douglas Ng, Blas Frangione, Bruce Kagan, Jorge Ghiso, Ratnesh Lal
Year
2005
Journal
PNAS
Abstract
Protein conformational diseases, including Alzheimer’s, Huntington’s, and Parkinson’s diseases, result from protein misfolding, giving a distinct fibrillar feature termed amyloid. Recent studies show that only the globular (not fibrillar) conformation of amyloid proteins is sufficient to induce cellular pathophysiology. However, the 3D structural conformations of these globular structures, a key missing link in designing effective prevention and treatment, remain undefined as of yet. By using atomic force microscopy, circular dichroism, gel electrophoresis, and electrophysiological recordings, we show here that an array of amyloid molecules, including amyloid- (1–40), -synuclein, ABri, ADan, serum amyloid A, and amylin undergo supramolecular conformational change. In reconstituted membranes, they form morphologically compatible ion-channel-like structures and elicit single ion-channel currents. These ion channels would destabilize cellular ionic homeostasis and hence induce cell pathophysiology and degeneration in amyloid diseases.
Full Article
Instrument
J-720
Keywords
Circular dichroism, Secondary structure, Biochemistry