%0 Journal Article
%A Sun, N.
%A Hartmann, R.
%A Lecher, J.
%A Stoldt, M.
%A Funke, S.A.
%A Gremer, L.
%A Ludwig, H.-H.
%A Demuth, H.U.
%A Kleinschmidt, H.
%A Willbold, D.
%T Structural analysis of the pyroglutamate modified isoform of the Alzheimer's disease related beta-amyloid using NMR spectroscopy
%J Journal of peptide science
%V 18
%@ 1075-2617
%C New York, NY [u.a.]
%I Wiley
%M PreJuSER-23150
%P 691 - 695
%D 2012
%Z Record converted from VDB: 12.11.2012
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23001756
%U <Go to ISI:>//WOS:000310029900006
%R 10.1002/psc.2456
%U https://juser.fz-juelich.de/record/23150