TY  - JOUR
AU  - Sun, N.
AU  - Hartmann, R.
AU  - Lecher, J.
AU  - Stoldt, M.
AU  - Funke, S.A.
AU  - Gremer, L.
AU  - Ludwig, H.-H.
AU  - Demuth, H.U.
AU  - Kleinschmidt, H.
AU  - Willbold, D.
TI  - Structural analysis of the pyroglutamate modified isoform of the Alzheimer's disease related beta-amyloid using NMR spectroscopy
JO  - Journal of peptide science
VL  - 18
SN  - 1075-2617
CY  - New York, NY [u.a.]
PB  - Wiley
M1  - PreJuSER-23150
SP  - 691 - 695
PY  - 2012
N1  - Record converted from VDB: 12.11.2012
AB  - The aggregation of the Aβ plays a fundamental role in the pathology of AD. Recently, N-terminally modified Aβ species, pE-Aβ, have been described as major constituents of Aβ deposits in the brains of AD patients. pE-Aβ has an increased aggregation propensity and shows increased toxicity compared with Aβ1-40 and Aβ1-42. In the present work, high-resolution NMR spectroscopy was performed to study pE-Aβ3-40 in aqueous TFE-containing solution. Two-dimensional TOCSY and NOESY experiments were performed. On the basis of NOE and chemical shift data, pE-Aβ3-40 was shown to contain two helical regions formed by residues 14-22 and 30-36. This is similar as previously described for Aβ1-40. However, the secondary chemical shift data indicate decreased helical propensity in pE-Aβ3-40 when compared with Aβ1-40 under exactly the same conditions. This is in agreement with the observation that pE-Aβ3-40 shows a drastically increased tendency to form β-sheet-rich structures under more physiologic conditions. Structural studies of pE-Aβ are crucial for better understanding the structural basis of amyloid fibril formation in the brain during development of AD, especially because an increasing number of reports indicate a decisive role of pE-Aβ for the pathogenesis of AD. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
LB  - PUB:(DE-HGF)16
C6  - pmid:23001756
UR  - <Go to ISI:>//WOS:000310029900006
DO  - DOI:10.1002/psc.2456
UR  - https://juser.fz-juelich.de/record/23150
ER  -