Conformational analysis of amyloid precursor protein fragment containing amino acids 667-676, and the effect of d-Asp and iso-Asp substitution at Asp 672 residue

Ganesh Shanmugam, Prasad L. Polavarapu, Emma Láng, Zsuzsa Majer

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5 Citations (Scopus)

Abstract

Amyloid precursor protein (APP) fragment containing amino acids 667-676, (APP 667-676), is a substrate for β-secretase which is responsible for generating amyloid β peptides. Conformational analysis of APP 667-676 peptide [Ac-Ser-Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-Arg-NH 2] and the effect of substitution of Asp 672 with d-Asp and iso-l-Asp, studied for the first time, demonstrate that the peptide backbone of APP 667-676 is flexible and adopts different conformations in different solvent environments (water, trifluoroethanol and dimethylsulfoxide). A major conformational difference was observed in trifluoroethanol solvent when Asp 672 is substituted with d-Asp and iso-Asp. These conformational changes involved in APP 667-676 may assist in understanding the interactions between β-secretase and APP 667-676, with relevance to Alzheimer's disease.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalJournal of Structural Biology
Volume177
Issue number3
DOIs
Publication statusPublished - Mar 1 2012

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Keywords

  • APP
  • Amyloid
  • Circular dichroism
  • D-Amino acid
  • Peptide
  • TFE

ASJC Scopus subject areas

  • Structural Biology

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