Mechanistic insight into the early stages of amyloid formation using an anuran peptide

Sourav Ray, Stephanie Holden, Lisandra L. Martin, Ajay Singh Panwar

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8 Citations (Scopus)


Uperin 3.5 is a short antimicrobial peptide consisting of 17 Amino acids (GVGDL5IRKAV10SVIKN15IV-NH2) and is naturally obtained from the skin secretion of Uperoleia mjobergii. It is unusual, as it does not aggregate in pure water, but self-aggregates to form amyloid fibrils in saline buffer. Hence, it can be used as a model peptide to understand the role of salt in the early stages of amyloid fibril formation. We use molecular dynamics simulations and direct experimental evidence from circular dichroism measurements to investigate the effect of NaCl concentration on interpeptide interactions during the early stages of uperin 3.5 aggregation in water. Our simulations show that addition of salt leads to screening of the positive charges on the R7, K8, and K14 residues by chloride counter-ions, which in turn results in an increase in the net attraction between the predominantly hydrophobic AVSVI segments of the polypeptide. With addition of salt, changes in interpeptide interactions are accompanied by significant conformational transitions from largely random coil structures in the absence of salt, to greater fractions of α-helical conformations at higher NaCl concentrations, resulting in greater peptide aggregation at higher NaCl concentrations. Analysis of circular dichroism spectra also shows a similar correlation between an increase in α-helical content and enhanced aggregation with addition of salt. Thus, the aggregation of uperin 3.5 peptides in presence of salt, results from the combined effects of electrostatic screening, enhanced interaction between hydrophobic residues, and the accompanying conformational changes that stabilize aggregate formation.

Original languageEnglish
Article numbere24120
Number of pages17
JournalPeptide Science
Issue number5
Publication statusPublished - 1 Sep 2019


  • amyloid
  • circular dichroism
  • molecular dynamics
  • peptide aggregation

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