Dynamic properties of pH-dependent structural organization of the amyloidogenic β-protein (1-40)

Alexander Rubinstein, Yuri L. Lyubchenko, Simon Sherman

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The structural organization of the amyloidogenic β-protein containing 40 amino acid residues (Aβ40) was studied by the high temperature molecular dynamics simulations in the acidic (pH ∼ 3) and basic (pH ∼ 8) pH regions. The obtained data suggest that the central Ala21-Gly29 segment of Aβ40 can adopt folded and partially unfolded structures. At the basic pH, this segment forms folded structures stabilized by electrostatic interactions and hydrogen bonds. At the acidic pH, it forms partially unfolded structures. Two other segments flanking to the central segment exhibit the propensity to adopt unstable interconverting α-helical, 310-helical and turn-like structures. One of these segments is comprised of the Ala30-Val36 residues at both of the considered pHs. The second segment is comprised of the Glu11-Phe20 at the basic pH and of the Glu11-Val24 residues at the acidic pHs. The revealed pH-dependent structuration of the Aβ40 allowed us to suggest a possible scenario for initial Aβ aggregation. According to this scenario, the occurrence of the partially unfolded states of the Ala21-Gly29 segment plays main role in the Aβ oligomerization process.

Original languageEnglish (US)
Pages (from-to)31-43
Number of pages13
JournalPrion
Volume3
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Alzheimer disease
  • Amyloid-β protein
  • Electrostatic interactions
  • Fibril
  • Molecular dynamics simulations
  • Oligomerization

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

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