000203194 001__ 203194 000203194 005__ 20210129220318.0 000203194 0247_ $$2doi$$a10.1016/j.jmb.2015.01.020 000203194 0247_ $$2ISSN$$a0022-2836 000203194 0247_ $$2ISSN$$a1089-8638 000203194 0247_ $$2WOS$$aWOS:000351798700016 000203194 0247_ $$2altmetric$$aaltmetric:3716685 000203194 0247_ $$2pmid$$apmid:25659910 000203194 037__ $$aFZJ-2015-05195 000203194 041__ $$aEnglish 000203194 082__ $$a570 000203194 1001_ $$0P:(DE-HGF)0$$aWördehoff, Michael M.$$b0 000203194 245__ $$aSingle Fibril Growth Kinetics of α-Synuclein 000203194 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2015 000203194 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1439275031_4232 000203194 3367_ $$2DataCite$$aOutput Types/Journal article 000203194 3367_ $$00$$2EndNote$$aJournal Article 000203194 3367_ $$2BibTeX$$aARTICLE 000203194 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000203194 3367_ $$2DRIVER$$aarticle 000203194 520__ $$aNeurodegenerative disorders associated with protein misfolding are fatal diseases that are caused by fibrillation of endogenous proteins such as α-synuclein (α-syn) in Parkinson's disease (PD) or amyloid-β in Alzheimer's disease. Fibrils of α-syn are a major pathological hallmark of PD and certain aggregation intermediates are postulated to cause synaptic failure and cell death of dopaminergic neurons in the substantia nigra. For the development of therapeutic approaches, the mechanistic understanding of the fibrillation process is essential. Here we report real-time observation of α-syn fibril elongation on a glass surface, imaged by total internal reflection fluorescence microscopy using thioflavin T fluorescence. Fibrillation on the glass surface occurred in the same time frame and yielded fibrils of similar length as fibrillation in solution. Time-resolved imaging of fibrillation on a single fibril level indicated that α-syn fibril elongation follows a stop-and-go mechanism; that is, fibrils either extend at a homogenous growth rate or stop to grow for variable time intervals. The fibril growth kinetics were compatible with a model featuring two states, a growth state and a stop state, which were approximately isoenergetic and interconverted with rate constants of ~ 1.5 × 10− 4 s− 1. In the growth state, α-syn monomers were incorporated into the fibril with a rate constant of 8.6 × 103 M− 1 s− 1. Fibril elongation of α-syn is slow compared to other amyloidogenic proteins. 000203194 536__ $$0G:(DE-HGF)POF3-553$$a553 - Physical Basis of Diseases (POF3-553)$$cPOF3-553$$fPOF III$$x0 000203194 588__ $$aDataset connected to CrossRef 000203194 7001_ $$0P:(DE-Juel1)157832$$aBannach, Oliver$$b1$$eCorresponding author$$ufzj 000203194 7001_ $$0P:(DE-Juel1)167315$$aShaykhalishahi, Hamed$$b2$$ufzj 000203194 7001_ $$0P:(DE-Juel1)162310$$aKulawik, Andreas$$b3$$ufzj 000203194 7001_ $$0P:(DE-HGF)0$$aSchiefer, Stephanie$$b4 000203194 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b5$$ufzj 000203194 7001_ $$00000-0003-4301-5416$$aHoyer, Wolfgang$$b6 000203194 7001_ $$0P:(DE-Juel1)131992$$aBirkmann, Eva$$b7 000203194 773__ $$0PERI:(DE-600)1355192-9$$a10.1016/j.jmb.2015.01.020$$gVol. 427, no. 6, p. 1428 - 1435$$n6 B$$p1428 - 1435$$tJournal of molecular biology$$v427$$x0022-2836$$y2015 000203194 8564_ $$uhttp://www.sciencedirect.com/science/article/pii/S0022283615000765# 000203194 8564_ $$uhttps://juser.fz-juelich.de/record/203194/files/W%C3%B6rdehoff%2C%20Bannach%2C%20Shaykhalishahi%2C%20Kulawik%2C%20Schiefer%2C%20Willbold%2C%20Hoyer%2C%20Birkmann_2015.pdf$$yRestricted 000203194 8564_ $$uhttps://juser.fz-juelich.de/record/203194/files/W%C3%B6rdehoff%2C%20Bannach%2C%20Shaykhalishahi%2C%20Kulawik%2C%20Schiefer%2C%20Willbold%2C%20Hoyer%2C%20Birkmann_2015.pdf?subformat=pdfa$$xpdfa$$yRestricted 000203194 909CO $$ooai:juser.fz-juelich.de:203194$$pVDB 000203194 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)157832$$aForschungszentrum Jülich GmbH$$b1$$kFZJ 000203194 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)167315$$aForschungszentrum Jülich GmbH$$b2$$kFZJ 000203194 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)162310$$aForschungszentrum Jülich GmbH$$b3$$kFZJ 000203194 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132029$$aForschungszentrum Jülich GmbH$$b5$$kFZJ 000203194 9131_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vPhysical Basis of Diseases$$x0 000203194 9141_ $$y2015 000203194 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000203194 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000203194 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ MOL BIOL : 2013 000203194 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000203194 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000203194 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000203194 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000203194 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000203194 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000203194 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000203194 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000203194 920__ $$lyes 000203194 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x0 000203194 980__ $$ajournal 000203194 980__ $$aVDB 000203194 980__ $$aI:(DE-Juel1)ICS-6-20110106 000203194 980__ $$aUNRESTRICTED 000203194 981__ $$aI:(DE-Juel1)IBI-7-20200312