The role of the Cys2-Cys7 disulfide bridge in the early steps of Islet amyloid polypeptide aggregation: A molecular dynamics study

The rupture of the Cys2-Cys7 disulfide bridge decreases the stability and increases the β-sheet content of early IAPP aggregates. Aggregation of Islet amyloid polypeptide (IAPP) is believed to play a critical role in the pathogenesis of Type II Diabetes Mellitus. In an attempt to gain details on the...

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Bibliographic Details
Published in:Chemical physics letters 2008-10, Vol.463 (4), p.396-399
Main Authors: Milardi, Danilo, Pappalardo, Matteo, Pannuzzo, Martina, Grasso, Domenico M., Rosa, Carmelo La
Format: Article
Language:English
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Summary:The rupture of the Cys2-Cys7 disulfide bridge decreases the stability and increases the β-sheet content of early IAPP aggregates. Aggregation of Islet amyloid polypeptide (IAPP) is believed to play a critical role in the pathogenesis of Type II Diabetes Mellitus. In an attempt to gain details on the early events of this process, here we performed MD simulations of the spontaneous assembly of three replicas of human IAPP. Systems containing the Cys2-Cys7 disulfide bridge exhibited a greater stability and a decreased tendency to evolve into β-sheet rich structures if compared to the disulfide-depleted variants. Conversely, the stability of assemblies constituted by the rat isoforms was shown to be independent from the presence of the disulfide bridge.
ISSN:0009-2614
1873-4448
DOI:10.1016/j.cplett.2008.07.110