Reversible random coil-beta-sheet transition of the Alzheimer beta-amyloid fragment (25-35)

Terzi, E. and Holzemann, G. and Seelig, J.. (1994) Reversible random coil-beta-sheet transition of the Alzheimer beta-amyloid fragment (25-35). Biochemistry, Vol. 33, H. 6. pp. 1345-1350.

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Official URL: http://edoc.unibas.ch/dok/A5257450

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The beta-amyloid protein (39-43 amino acid residues) is the major constituent of the amyloid deposits found in brain of patients with Alzheimer's disease. Using circular dichroism spectroscopy, we have studied the secondary structure and the aggregation of fragment 25-35 of the beta-amyloid protein (beta AP(25-35)OH) under a variety of conditions. beta AP(25-35)OH in solution at pH 4.0 or 5.5 exhibits a concentration-dependent random coilbeta-sheet transition. The equilibrium is characterized spectroscopically by an isodichroic point and can be described quantitatively by a simple association model with association constants between 1.8 x 10(4) M-1 (non-cooperative model, nucleation parameter sigma = 1) and 2.9 x 10(4) M-1 (cooperative model, sigma = 0.2). The enthalpy of association is delta H approximately -3 kcal/mol as determined by titration calorimetry. The equilibrium is shifted completely toward beta-structured fibrils at pH 7.4 where the Met-35 carboxyl group is fully charged. In contrast, removal of the charged carboxy terminus by amidation locks the equilibrium in the random coil conformation. Model calculations suggest an antiparallel beta-sheet structure involving residues 28-35 which is stabilized at both ends of the beta-sheet by ion pairs formed between Lys-28 and Met-35. Removal of fibrils via millipore filtration leads to solutions with random coil monomers only. Seeding these solutions with a few fibrils establishes a new random coilbeta-sheet equilibrium.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig J)
UniBasel Contributors:Seelig, Joachim
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:19
Deposited On:22 Mar 2012 13:18

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