TY  - JOUR
AU  - Gruning, C. S. R.
AU  - Klinker, S.
AU  - Wolff, M.
AU  - Schneider, M.
AU  - Toksöz, K.
AU  - Klein, A. N.
AU  - Nagel-Steger, L.
AU  - Willbold, D.
AU  - Hoyer, W.
TI  - The Off-rate of Monomers Dissociating from Amyloid-ß Protofibrils
JO  - The journal of biological chemistry
VL  - 288
IS  - 52
SN  - 1083-351X
CY  - Bethesda, Md.
PB  - Soc.
M1  - FZJ-2014-00261
SP  - 37104 - 37111
PY  - 2013
AB  - The interconversion of monomers, oligomers, and amyloid fibrils of the amyloid-peptide (A) has been implicated in the pathogenesis of Alzheimer disease. The determination of the kinetics of the individual association and dissociation reactions is hampered by the fact that forward and reverse reactions to/from different aggregation states occur simultaneously. Here, we report the kinetics of dissociation of A Monomers from protofibrils, prefibrillar high molecular weight oligomers previously shown to possess pronounced neurotoxicity. An engineered binding protein sequestering specifically mono-meric A was employed to follow protofibril dissociation by tryptophan fluorescence, precluding confounding effects of reverse or competing reactions. A protofibril dissociation into monomers follows exponential decay kinetics with a time constant of ~2 h at 25 °C and an activation energy of 80 kJ/mol, values typical for high affinity biomolecular interactions. This study demonstrates the high kinetic stability of A protofibrils toward dissociation into monomers and supports the delineation of the A folding and assembly energy landscape.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000329189700030
DO  - DOI:10.1074/jbc.M113.513432
UR  - https://juser.fz-juelich.de/record/141924
ER  -