Solid-state NMR analysis of the ?-strand orientation of the protofibrils of amyloid ?-protein
30 November 2012
Publication year: 2012
Source:Biochemical and Biophysical Research Communications, Volume 428, Issue 4
Alzheimer’s disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid ?-protein (A?42) in the brain. During the process of fibrillation, the A?42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A?42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A?42 protofibrils was analyzed by 13C–13C rotational resonance experiments in the solid state. Unlike the A?42 fibrils, an intermolecular 13C–13C correlation was not found in the A?42 protofibrils. This result suggests that the ?-strands of the A?42 protofibrils are not in an in-register parallel orientation. A?42 monomers would assemble to form protofibrils with the ?-strand conformation, then transform into fibrils by forming intermolecular parallel ?-sheets.
Highlights
? The supramolecular structure of A?42 protofibrils was analyzed by solid-state NMR. ? The Ala-21 residue in the A?42 protofibrils is included in a slightly disordered ?-strand. ? The A?42 protofibrils do not form intermolecular in-register parallel ?-sheets.
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