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bioRxiv · 10.1101/2020.03.09.984336

D-Retro Inverso (DRI) Amylin and the Stability of Amylin Fibrils

Pnadey, P.·Nguyen, N.·Hansmann, U. H. E.
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Abstract

Motivated by the role that amylin aggregates pay in type-II diabetes, we compare the stability of regular amylin fibrils with the stability of fibrils where L-amino acid chains are replaced by D-Retro Inverso (DRI) amylin, i.e., peptides where the sequence of amino acids is reversed, and at the same time the L-amino acids are replaced by their mirror images. Our molecular dynamics simulations show that despite leading to only marginal difference in fibril structure and stability, aggregating DRI-amylin peptides have different pattern of contacts and hydrogen bonding. Because of these differences does DRI-amylin, when interacting with regular (L) amylin, alter the elongation process and lowers the stability of hybrid amylin fibrils. Our results suggest not only a potential use of DRI-amylin as inhibitor of amylin fibril-formation, but points also to the possibility of using insertion of DRI-proteins in L-assemblies as a way to probe the role of certain kinds of hydrogen bonds in supra-molecular assemblies or aggregates.

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Pnadey, P., Nguyen, N., Hansmann, U. H. E.. 2020-03-11. D-Retro Inverso (DRI) Amylin and the Stability of Amylin Fibrils. https://doi.org/10.1101/2020.03.09.984336

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