Journal
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY
Volume 1476, Issue 1, Pages 93-102Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0167-4838(99)00228-9
Keywords
Alzheimer's disease; circular dichroism; folding intermediate; hydrophobic interaction
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Funding
- NHLBI NIH HHS [HL61429, HL26335] Funding Source: Medline
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To probe the role of temperature in the conversion of soluble Alzheimer's beta-amyloid peptide (A beta) to insoluble beta-sheet rich aggregates, we analyzed the solution conformation of A beta(1-40) from 0 to 98 degrees C by far-UV circular dichroism (CD) and native gel electrophoresis. The CD spectra of 15-300 mu g/ml A beta(1-40) in aqueous solution (pH similar to 4.6) at 0 degrees C are concentration-independent and suggest a substantially unfolded and/or unusually folded conformation characteristic of A beta monomer or dimer. Heating from 0 to 37 degrees C induces a rapid reversible coil to beta-strand transition that is independent of the peptide concentration and thus is not linked to oligomerization. Consequently, this transition may occur within the A beta(1-40) monomer or dimer. Incubation at 37 degrees C leads to slow reversible concentration-dependent beta-sheet accumulation; heating to 85 degrees C induces further beta-sheet folding and oligomerization. Our results demonstrate the importance of temperature and thermal history for the conformation of A beta. (C) 2000 Elsevier Science B.V. All rights reserved.
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