Probing the Effect of Amino-Terminal Truncation for Aβ1−40 Peptides

Publisher Website
Google Scholar
Abstract
We examine the effect of deletion of the amino-terminal (residues 1−9) on the structure and energetics of Aβ1−40 peptides. To this end, we use replica exchange molecular dynamics to compare the conformational ensembles of Aβ1−40 and amino-truncated Aβ10−40 monomers and dimers. Overall, the deletion of the amino-terminal appears to cause minor structural and energetic changes in Aβ monomers and dimers. More specifically, our findings are as follows: (1) there is a small but discernible conversion of β-strand structure into helix upon amino-terminal deletion, (2) secondary structure changes due to truncation are caused by missing side chain interactions formed by the amino-terminal, and (3) the amino-terminal together with the central sequence region (residues 10−23) represents the primary aggregation interface in Aβ1−40 dimers. The amino-truncated Aβ10−40 retains this aggregation interface, which is reduced to the central sequence region. We argue that the analysis of available experimental data supports our conclusions. Our findings also suggest that amino-truncated Aβ10−40 peptide is an adequate model for studying Aβ1−40 aggregation.