Matches in SemOpenAlex for { <https://semopenalex.org/work/W2969101038> ?p ?o ?g. }
- W2969101038 abstract "Abstract As an intrinsically disordered protein, monomeric alpha synuclein (aSyn) constantly reconfigures and probes the conformational space. Long-range interactions across the protein maintain its solubility and mediate this dynamic flexibility, but also provide residual structure. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of monomeric conformations is difficult. Herein, we used the biologically relevant calcium ion to investigate the conformation of monomeric aSyn in relation to its aggregation propensity. By using calcium to perturb the conformational ensemble, we observe differences in structure and intra-molecular dynamics between two aSyn C-terminal variants, D121A and pS129, and the aSyn familial disease mutants, A30P, E46K, H50Q, G51D, A53T and A53E, compared to wild-type (WT) aSyn. We observe that the more exposed the N-terminus and the beginning of the NAC region are, the more aggregation prone monomeric aSyn conformations become. N-terminus exposure occurs upon release of C-terminus interactions when calcium binds, but the level of exposure is specific to the aSyn mutation present. There was no correlation between single charge alterations, calcium affinity, or the number of ions bound on aSyn’s aggregation propensity, indicating that sequence or post-translation modification (PTM)-specific conformational differences between the N- and C-termini and the specific local environment mediate aggregation propensity instead. Understanding aggregation prone conformations of monomeric aSyn and the environmental conditions they form under will allow us to design new therapeutics targeted to the monomeric protein, to stabilise aSyn in non-aggregation prone conformations, by either preserving long-range interactions between the N- and C-termini or by protecting the N-terminus from exposure." @default.
- W2969101038 created "2019-08-22" @default.
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- W2969101038 date "2019-08-20" @default.
- W2969101038 modified "2023-10-02" @default.
- W2969101038 title "Extent of N-terminus exposure by altered long-range interactions of monomeric alpha-synuclein determines its aggregation propensity" @default.
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- W2969101038 cites W1952861039 @default.
- W2969101038 cites W1965778124 @default.
- W2969101038 cites W1973980288 @default.
- W2969101038 cites W1974906361 @default.
- W2969101038 cites W1977044612 @default.
- W2969101038 cites W1986580794 @default.
- W2969101038 cites W1992251315 @default.
- W2969101038 cites W2006199861 @default.
- W2969101038 cites W2011077381 @default.
- W2969101038 cites W2012534156 @default.
- W2969101038 cites W2023245921 @default.
- W2969101038 cites W2025153638 @default.
- W2969101038 cites W2031964854 @default.
- W2969101038 cites W2038431361 @default.
- W2969101038 cites W2046263328 @default.
- W2969101038 cites W2049817931 @default.
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- W2969101038 cites W2076344926 @default.
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- W2969101038 cites W2080751623 @default.
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- W2969101038 cites W2089435862 @default.
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- W2969101038 cites W2139506875 @default.
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- W2969101038 cites W2144972310 @default.
- W2969101038 cites W2149804748 @default.
- W2969101038 cites W2150656456 @default.
- W2969101038 cites W2164233055 @default.
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- W2969101038 cites W2546834208 @default.
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- W2969101038 doi "https://doi.org/10.1101/740241" @default.
- W2969101038 hasPublicationYear "2019" @default.
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