{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ruzafa D"],"funding":["Universidad de Granada","Ministerio de Economía y Competitividad","Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía","European Regional Development Fund (ES)"],"pagination":["e0178576"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5451137"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(5)"],"pubmed_abstract":["The biological function of α-Synuclein has been related to binding to lipids and membranes but these interactions can also mediate α-Synuclein aggregation, which is associated to Parkinson's disease and other neuropathologies. In brain tissue α-Synuclein is constitutively N-acetylated, a modification that plays an important role in its conformational propensity, lipid and membrane binding, and aggregation propensity. We studied the interactions of the lipid-mimetic SDS with N-acetylated and non-acetylated α-Synuclein, as well as their early-onset Parkinson's disease variants A30P, E46K and A53T. At low SDS/protein ratios α-Synuclein forms oligomeric complexes with SDS micelles with relatively low α-helical structure. These micellar oligomers can efficiently nucleate aggregation of monomeric α-Synuclein, with successive formation of oligomers, protofibrils, curly fibrils and mature amyloid fibrils. N-acetylation reduces considerably the rate of aggregation of WT α-Synuclein. However, in presence of any of the early-onset Parkinson's disease mutations the protective effect of N-acetylation against micelle-induced aggregation becomes impaired. At higher SDS/protein ratios, N-acetylation favors another conformational transition, in which a second type of α-helix-rich, non-aggregating oligomers become stabilized. Once again, the Parkinson's disease mutations disconnect the influence of N-acetylation in promoting this transition. These results suggest a cooperative link between the N-terminus and the region of the mutations that may be important for α-Synuclein function."],"journal":["PloS one"],"pubmed_title":["The influence of N-terminal acetylation on micelle-induced conformational changes and aggregation of α-Synuclein."],"pmcid":["PMC5451137"],"funding_grant_id":["BIO2013-40697-R","BIO2009-07317","PP2012-PI06","FQM-02838"],"pubmed_authors":["Ruzafa D","Morel B","Bisello G","Broersen K","Hernandez-Gomez YS","Conejero-Lara F"],"additional_accession":[]},"is_claimable":false,"name":"The influence of N-terminal acetylation on micelle-induced conformational changes and aggregation of α-Synuclein.","description":"The biological function of α-Synuclein has been related to binding to lipids and membranes but these interactions can also mediate α-Synuclein aggregation, which is associated to Parkinson's disease and other neuropathologies. In brain tissue α-Synuclein is constitutively N-acetylated, a modification that plays an important role in its conformational propensity, lipid and membrane binding, and aggregation propensity. We studied the interactions of the lipid-mimetic SDS with N-acetylated and non-acetylated α-Synuclein, as well as their early-onset Parkinson's disease variants A30P, E46K and A53T. At low SDS/protein ratios α-Synuclein forms oligomeric complexes with SDS micelles with relatively low α-helical structure. These micellar oligomers can efficiently nucleate aggregation of monomeric α-Synuclein, with successive formation of oligomers, protofibrils, curly fibrils and mature amyloid fibrils. N-acetylation reduces considerably the rate of aggregation of WT α-Synuclein. However, in presence of any of the early-onset Parkinson's disease mutations the protective effect of N-acetylation against micelle-induced aggregation becomes impaired. At higher SDS/protein ratios, N-acetylation favors another conformational transition, in which a second type of α-helix-rich, non-aggregating oligomers become stabilized. Once again, the Parkinson's disease mutations disconnect the influence of N-acetylation in promoting this transition. These results suggest a cooperative link between the N-terminus and the region of the mutations that may be important for α-Synuclein function.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017","modification":"2025-04-19T19:07:00.223Z","creation":"2019-03-26T22:46:22Z"},"accession":"S-EPMC5451137","cross_references":{"pubmed":["28562630"],"doi":["10.1371/journal.pone.0178576"]}}