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@ARTICLE{Gruning:141924,
author = {Gruning, C. S. R. and Klinker, S. and Wolff, M. and
Schneider, M. and Toksöz, K. and Klein, A. N. and
Nagel-Steger, L. and Willbold, D. and Hoyer, W.},
title = {{T}he {O}ff-rate of {M}onomers {D}issociating from
{A}myloid-ß {P}rotofibrils},
journal = {The journal of biological chemistry},
volume = {288},
number = {52},
issn = {1083-351X},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {FZJ-2014-00261},
pages = {37104 - 37111},
year = {2013},
abstract = {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.},
cin = {ICS-6},
ddc = {570},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {452 - Structural Biology (POF2-452)},
pid = {G:(DE-HGF)POF2-452},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000329189700030},
doi = {10.1074/jbc.M113.513432},
url = {https://juser.fz-juelich.de/record/141924},
}