Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?

M ColesD J Craik


The three-dimensional solution structure of the 40 residue amyloid beta-peptide, Abeta(1-40), has been determined using NMR spectroscopy at pH 5.1, in aqueous sodium dodecyl sulfate (SDS) micelles. In this environment, which simulates to some extent a water-membrane medium, the peptide is unstructured between residues 1 and 14 which are mainly polar and likely solvated by water. However, the rest of the protein adopts an alpha-helical conformation between residues 15 and 36 with a kink or hinge at 25-27. This largely hydrophobic region is likely solvated by SDS. Based on the derived structures, evidence is provided in support of a possible new location for the transmembrane domain of Abeta within the amyloid precursor protein (APP). Studies between pH 4.2 and 7.9 reveal a pH-dependent helix-coil conformational switch. At the lower pH values, where the carboxylate residues are protonated, the helix is uncharged, intact, and lipid-soluble. As the pH increases above 6. 0, part of the helical region (15-24) becomes less structured, particularly near residues E22 and D23 where deprotonation appears to facilitate unwinding of the helix. This pH-dependent unfolding to a random coil conformation precedes any tendency of this peptide to...Continue Reading


Nov 1, 1992·Journal of Biomolecular NMR·M PiottoV Sklenár
Jun 5, 1988·Journal of Molecular Biology·D J Barlow, J M Thornton
Dec 1, 1994·Biophysical Journal·S R DurellH B Pollard
Oct 1, 1995·European Journal of Biochemistry·H StichtP Rösch
Sep 1, 1995·Journal of Biomolecular NMR·D S WishartB D Sykes
Apr 1, 1996·European Journal of Biochemistry·L Hendriks, C Van Broeckhoven
May 6, 1996·Biochemical and Biophysical Research Communications·R P MasonP E Mason
Aug 22, 1997·The Journal of Biological Chemistry·W Garzon-RodriguezC G Glabe
Oct 1, 1995·Journal of Biomolecular Structure & Dynamics·Dimuthu JayawickramaCynthia K Larive

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