Determination of amino acids that favour the αL region using Ramachandran propensity plots. Implications for α-sheet as the possible amyloid intermediate

Hayward, Steven and Milner-White, E. James (2021) Determination of amino acids that favour the αL region using Ramachandran propensity plots. Implications for α-sheet as the possible amyloid intermediate. Journal of Structural Biology, 213 (2). ISSN 1047-8477

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Abstract

In amyloid diseases an insoluble amyloid fibril forms via a soluble oligomeric intermediate. It is this intermediate that mediates toxicity and it has been suggested, somewhat controversially, that it has the α-sheet structure. Nests and α-strands are similar peptide motifs in that alternate residues lie in the αR and γL regions of the Ramachandran plot for nests, or αR and αL regions for α-strands. In nests a concavity is formed by the main chain NH atoms whereas in α-strands the main chain is almost straight. Using “Ramachandran propensity plots” to focus on the αL/γL region, it is shown that glycine favours γL (82% of amino acids are glycine), but disfavours αL (3% are glycine). Most charged and polar amino acids favour αL with asparagine having by far the highest propensity. Thus, glycine favours nests but, contrary to common expectation, should not favour α-sheet. By contrast most charged or polar amino acids should favour α-sheet by their propensity for the αL conformation, which is more discriminating amongst amino acids than the αR conformation. Thus, these results suggest the composition of sequences that favour α-sheet formation and point towards effective prediction of α-sheet from sequence.

Item Type: Article
Faculty \ School: Faculty of Science > School of Computing Sciences
Depositing User: LivePure Connector
Date Deposited: 09 Apr 2021 23:49
Last Modified: 09 Jul 2021 07:20
URI: https://ueaeprints.uea.ac.uk/id/eprint/79655
DOI: 10.1016/j.jsb.2021.107738

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