000912257 001__ 912257 000912257 005__ 20230308081538.0 000912257 0247_ $$2doi$$a10.1038/s41467-022-34552-7 000912257 0247_ $$2Handle$$a2128/33447 000912257 0247_ $$2pmid$$a36357403 000912257 0247_ $$2WOS$$aWOS:000881814200030 000912257 037__ $$aFZJ-2022-05454 000912257 082__ $$a500 000912257 1001_ $$0P:(DE-Juel1)172887$$aFrieg, Benedikt$$b0 000912257 245__ $$aThe 3D structure of lipidic fibrils of α-synuclein 000912257 260__ $$a[London]$$bNature Publishing Group UK$$c2022 000912257 3367_ $$2DRIVER$$aarticle 000912257 3367_ $$2DataCite$$aOutput Types/Journal article 000912257 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1677056899_20615 000912257 3367_ $$2BibTeX$$aARTICLE 000912257 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000912257 3367_ $$00$$2EndNote$$aJournal Article 000912257 520__ $$aα-synuclein misfolding and aggregation into fibrils is a common feature of α-synucleinopathies, such as Parkinson’s disease, in which α-synuclein fibrils are a characteristic hallmark of neuronal inclusions called Lewy bodies. Studies on the composition of Lewy bodies extracted postmortem from brain tissue of Parkinson’s patients revealed that lipids and membranous organelles are also a significant component. Interactions between α-synuclein and lipids have been previously identified as relevant for Parkinson’s disease pathology, however molecular insights into their interactions have remained elusive. Here we present cryo-electron microscopy structures of six α-synuclein fibrils in complex with lipids, revealing specific lipid-fibril interactions. We observe that phospholipids promote an alternative protofilament fold, mediate an unusual arrangement of protofilaments, and fill the central cavities of the fibrils. Together with our previous studies, these structures also indicate a mechanism for fibril-induced lipid extraction, which is likely to be involved in the development of α-synucleinopathies. Specifically, one potential mechanism for the cellular toxicity is the disruption of intracellular vesicles mediated by fibrils and oligomers, and therefore the modulation of these interactions may provide a promising strategy for future therapeutic interventions. 000912257 536__ $$0G:(DE-HGF)POF4-5244$$a5244 - Information Processing in Neuronal Networks (POF4-524)$$cPOF4-524$$fPOF IV$$x0 000912257 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de 000912257 7001_ $$00000-0001-9948-7493$$aAntonschmidt, Leif$$b1 000912257 7001_ $$00000-0002-2172-5110$$aDienemann, Christian$$b2 000912257 7001_ $$0P:(DE-Juel1)176479$$aGeraets, James A.$$b3 000912257 7001_ $$0P:(DE-HGF)0$$aNajbauer, Eszter E.$$b4 000912257 7001_ $$0P:(DE-HGF)0$$aMatthes, Dirk$$b5 000912257 7001_ $$00000-0003-3570-3534$$ade Groot, Bert L.$$b6 000912257 7001_ $$00000-0003-3216-9065$$aAndreas, Loren B.$$b7 000912257 7001_ $$00000-0003-2041-5740$$aBecker, Stefan$$b8 000912257 7001_ $$00000-0002-1266-4344$$aGriesinger, Christian$$b9$$eCorresponding author 000912257 7001_ $$0P:(DE-Juel1)132018$$aSchröder, Gunnar F.$$b10$$eCorresponding author 000912257 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-022-34552-7$$gVol. 13, no. 1, p. 6810$$n1$$p6810$$tNature Communications$$v13$$x2041-1723$$y2022 000912257 8564_ $$uhttps://juser.fz-juelich.de/record/912257/files/1200190759_SN-2022-00734-B_Invoice_Gold%20OA%20Springer.pdf 000912257 8564_ $$uhttps://juser.fz-juelich.de/record/912257/files/The%203D%20structure%20of%20lipidic%20fibrils.pdf$$yOpenAccess 000912257 8767_ $$8SN-2022-00734-b$$92023-02-21$$a1200190759$$d2022-01-18$$eAPC$$jZahlung erfolgt$$lDEAL: Springer 000912257 909CO $$ooai:juser.fz-juelich.de:912257$$pdnbdelivery$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire 000912257 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)172887$$aForschungszentrum Jülich$$b0$$kFZJ 000912257 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132018$$aForschungszentrum Jülich$$b10$$kFZJ 000912257 9131_ $$0G:(DE-HGF)POF4-524$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5244$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vMolecular and Cellular Information Processing$$x0 000912257 9141_ $$y2022 000912257 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2021-02-02 000912257 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-02 000912257 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2021-02-02 000912257 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000912257 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-02 000912257 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000912257 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-02 000912257 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2021$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-10-13T14:44:21Z 000912257 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-10-13T14:44:21Z 000912257 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review$$d2021-10-13T14:44:21Z 000912257 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2022-11-11 000912257 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bNAT COMMUN : 2021$$d2022-11-11 000912257 915pc $$0PC:(DE-HGF)0000$$2APC$$aAPC keys set 000912257 915pc $$0PC:(DE-HGF)0001$$2APC$$aLocal Funding 000912257 915pc $$0PC:(DE-HGF)0002$$2APC$$aDFG OA Publikationskosten 000912257 915pc $$0PC:(DE-HGF)0003$$2APC$$aDOAJ Journal 000912257 920__ $$lyes 000912257 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x0 000912257 980__ $$ajournal 000912257 980__ $$aVDB 000912257 980__ $$aI:(DE-Juel1)IBI-7-20200312 000912257 980__ $$aAPC 000912257 980__ $$aUNRESTRICTED 000912257 9801_ $$aAPC 000912257 9801_ $$aFullTexts