Probing the effect of amino-terminal truncation for Abeta1-40 peptides.
We examine the effect of deletion of the amino-terminal (residues 1-9) on the structure and energetics of Abeta1-40 peptides. To this end, we use replica exchange molecular dynamics to compare the conformational ensembles of Abeta1-40 and amino-truncated Abeta10-40 monomers and dimers. Overall, the deletion of the amino-terminal appears to cause minor structural and energetic changes in Abeta monomers and dimers. More specifically, our findings are as follows: (1) there is a small but discernible conversion of beta-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 Abeta1-40 dimers. The amino-truncated Abeta10-40 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 Abeta10-40 peptide is an adequate model for studying Abeta1-40 aggregation.
Department of Bioinformatics and Computational Biology, George Mason University, Manassas, Virginia 20110, USA.
Takako
T
Takeda
Dmitri K
DK
Klimov
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D013816:Thermodynamics
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)