A conformation change in the carboxyl terminus of Alzheimer's A beta(1-40)accompanies the transition from dimer to fibril as revealed by fluorescence quenching analysis
W. Garzon-rodriguez et al., A conformation change in the carboxyl terminus of Alzheimer's A beta(1-40)accompanies the transition from dimer to fibril as revealed by fluorescence quenching analysis, J BIOL CHEM, 275(30), 2000, pp. 22645-22649
Alzheimer's disease is characterized by the presence of insoluble, fibrous
deposits composed principally of amyloid beta (A beta) peptide. A number of
studies have provided information on the fibril structure and on the facto
rs affecting fiber formation, but the details of the fibril structure are n
ot known. We used fluorescence quenching to investigate the solvent accessi
bility and surface charge of the soluble A beta(1-40) dimer and amyloid fib
rils, Analogs of A beta(1-40) containing a single tryptophan were synthesiz
ed by substituting residues at positions 4, 10, 34, and 40 with tryptophan,
Quenching measurements in the dimeric state indicate that the amino-termin
al analogs (A beta F4W and A beta Y10W) are accessible to polar quenchers,
and the more carboxyl-terminal analog A beta V34W is less accessible. A bet
a V40W, on the other hand, exhibits a low degree of quenching, indicating t
hat this residue is highly shielded from the solvent in the dimeric state.
Correcting for the effect of reduced translational and rotational diffusion
, fibril formation was associated with a selective increase in solvent expo
sure of residues 34 and 40, suggesting that a conformation change may take
place in the carboxyl-terminal region coincident with the dimer to fibril t
ransition.