% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Frieg:912257, author = {Frieg, Benedikt and Antonschmidt, Leif and Dienemann, Christian and Geraets, James A. and Najbauer, Eszter E. and Matthes, Dirk and de Groot, Bert L. and Andreas, Loren B. and Becker, Stefan and Griesinger, Christian and Schröder, Gunnar F.}, title = {{T}he 3{D} structure of lipidic fibrils of α-synuclein}, journal = {Nature Communications}, volume = {13}, number = {1}, issn = {2041-1723}, address = {[London]}, publisher = {Nature Publishing Group UK}, reportid = {FZJ-2022-05454}, pages = {6810}, year = {2022}, abstract = {α-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.}, cin = {IBI-7}, ddc = {500}, cid = {I:(DE-Juel1)IBI-7-20200312}, pnm = {5244 - Information Processing in Neuronal Networks (POF4-524)}, pid = {G:(DE-HGF)POF4-5244}, typ = {PUB:(DE-HGF)16}, pubmed = {36357403}, UT = {WOS:000881814200030}, doi = {10.1038/s41467-022-34552-7}, url = {https://juser.fz-juelich.de/record/912257}, }