Side-chain dynamics reveals transient association of Aβ(1-40) monomers with amyloid fibers.

ABSTRACT: Low-lying excited states that correspond to rare conformations or transiently bound species have been hypothesized to play an important role for amyloid nucleation. Despite their hypothesized importance in amyloid formation, transiently occupied states have proved difficult to detect directly. To experimentally characterize these invisible states, we performed a series of Carr-Purcell-Meiboom-Gill (CPMG)-based relaxation dispersion NMR experiments for the amyloidogenic Aβ(1-40) peptide implicated in Alzheimer's disease. Significant relaxation dispersion of the resonances corresponding to the side-chain amides of Q15 and N27 was detected before the onset of aggregation. The resonances corresponding to the peptide backbone did not show detectable relaxation dispersion, suggesting an exchange

SUBMITTER: Krishnamoorthy J 

PROVIDER: S-EPMC3535185 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature