000048163 001__ 48163
000048163 005__ 20210121114455.0
000048163 0247_ $$2doi$$a10.1038/srep16696
000048163 0248_ $$2sideral$$a93269
000048163 037__ $$aART-2015-93269
000048163 041__ $$aeng
000048163 100__ $$aTosatto, L.
000048163 245__ $$aSingle-molecule FRET studies on alpha-synuclein oligomerization of Parkinson's disease genetically related mutants
000048163 260__ $$c2015
000048163 5060_ $$aAccess copy available to the general public$$fUnrestricted
000048163 5203_ $$aOligomers of alpha-synuclein are toxic to cells and have been proposed to play a key role in the etiopathogenesis of Parkinson''s disease. As certain missense mutations in the gene encoding for alpha-synuclein induce early-onset forms of the disease, it has been suggested that these variants might have an inherent tendency to produce high concentrations of oligomers during aggregation, although a direct experimental evidence for this is still missing. We used single-molecule Förster Resonance Energy Transfer to visualize directly the protein self-assembly process by wild-type alpha-synuclein and A53T, A30P and E46K mutants and to compare the structural properties of the ensemble of oligomers generated. We found that the kinetics of oligomer formation correlates with the natural tendency of each variant to acquire beta-sheet structure. Moreover, A53T and A30P showed significant differences in the averaged FRET efficiency of one of the two types of oligomers formed compared to the wild-type oligomers, indicating possible structural variety among the ensemble of species generated. Importantly, we found similar concentrations of oligomers during the lag-phase of the aggregation of wild-type and mutated alpha-synuclein, suggesting that the properties of the ensemble of oligomers generated during self-assembly might be more relevant than their absolute concentration for triggering neurodegeneration.
000048163 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000048163 590__ $$a5.228$$b2015
000048163 591__ $$aMULTIDISCIPLINARY SCIENCES$$b7 / 62 = 0.113$$c2015$$dQ1$$eT1
000048163 592__ $$a2.034$$b2015
000048163 593__ $$aMultidisciplinary$$c2015$$dQ1
000048163 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000048163 700__ $$aHorrocks, M.H.
000048163 700__ $$aDear, A.J.
000048163 700__ $$aKnowles, T.P.J.
000048163 700__ $$aDalla Serra, M.
000048163 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza
000048163 700__ $$aDobson, C.M.
000048163 700__ $$aKlenerman, D.
000048163 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000048163 773__ $$g5 (2015), 16696 [12 pp]$$pSci. rep.$$tScientific Reports$$x2045-2322
000048163 8564_ $$s1520975$$uhttps://zaguan.unizar.es/record/48163/files/texto_completo.pdf$$yVersión publicada
000048163 8564_ $$s111100$$uhttps://zaguan.unizar.es/record/48163/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000048163 909CO $$ooai:zaguan.unizar.es:48163$$particulos$$pdriver
000048163 951__ $$a2021-01-21-10:48:05
000048163 980__ $$aARTICLE