{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:50:22Z","timestamp":1792108222113,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1038\/s41594-026-01879-4","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:02:33Z","timestamp":1788166953000},"page":"1479-1490","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Repositioning of polyubiquitin alters the pathologic tau filament structure"],"prefix":"10.1038","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-656X","authenticated-orcid":false,"given":"Ryohei","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Creekmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-9201","authenticated-orcid":false,"given":"Nabil F.","family":"Darwich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Baltazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Salphati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Changolkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevt\u2019her","family":"Hoxha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"O\u2019Rourke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2812-983X","authenticated-orcid":false,"given":"George M.","family":"Burslem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia M.-Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-473X","authenticated-orcid":false,"given":"Yi-Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-1180","authenticated-orcid":false,"given":"Edward B.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"1879_CR1","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41586-023-06437-2","volume":"621","author":"SHW Scheres","year":"2023","unstructured":"Scheres, S. H. W., Ryskeldi-Falcon, B. & Goedert, M. Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids. Nature 621, 701\u2013710 (2023).","journal-title":"Nature"},{"key":"1879_CR2","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1107\/S2059798319016577","volume":"76","author":"SHW Scheres","year":"2020","unstructured":"Scheres, S. H. W. Amyloid structure determination in RELION-3.1. Acta Crystallogr. D Struct. Biol. 76, 94\u2013101 (2020).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"1879_CR3","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41586-019-1026-5","volume":"568","author":"B Falcon","year":"2019","unstructured":"Falcon, B. et al. Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature 568, 420\u2013423 (2019).","journal-title":"Nature"},{"key":"1879_CR4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2306767120","volume":"120","author":"C Qi","year":"2023","unstructured":"Qi, C. et al. Tau filaments from amyotrophic lateral sclerosis\/parkinsonism-dementia complex adopt the CTE fold. Proc. Natl Acad. Sci. USA 120, e2306767120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1879_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01565-2","volume":"11","author":"C Qi","year":"2023","unstructured":"Qi, C. et al. Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy. Acta Neuropathol. Commun. 11, 74 (2023).","journal-title":"Acta Neuropathol. Commun."},{"key":"1879_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02741-x","volume":"147","author":"C Qi","year":"2024","unstructured":"Qi, C. et al. Tau filaments with the chronic traumatic encephalopathy fold in a case of vacuolar tauopathy with VCP mutation D395G. Acta Neuropathol. 147, 86 (2024).","journal-title":"Acta Neuropathol."},{"key":"1879_CR7","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature23002","volume":"547","author":"AWP Fitzpatrick","year":"2017","unstructured":"Fitzpatrick, A. W. P. et al. Cryo-EM structures of tau filaments from Alzheimer\u2019s disease. Nature 547, 185\u2013190 (2017).","journal-title":"Nature"},{"key":"1879_CR8","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1084\/jem.20160833","volume":"213","author":"JL Guo","year":"2016","unstructured":"Guo, J. L. et al. Unique pathological tau conformers from Alzheimer\u2019s brains transmit tau pathology in nontransgenic mice. J. Exp. Med. 213, 2635\u20132654 (2016).","journal-title":"J. Exp. Med."},{"key":"1879_CR9","doi-asserted-by":"publisher","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","volume":"37","author":"S Narasimhan","year":"2017","unstructured":"Narasimhan, S. et al. Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J. Neurosci. 37, 11406\u201311423 (2017).","journal-title":"J. Neurosci."},{"key":"1879_CR10","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.cell.2020.01.027","volume":"180","author":"T Arakhamia","year":"2020","unstructured":"Arakhamia, T. et al. Posttranslational modifications mediate the structural diversity of tauopathy strains. Cell 180, 633\u2013644 (2020).","journal-title":"Cell"},{"key":"1879_CR11","doi-asserted-by":"publisher","first-page":"eaay8826","DOI":"10.1126\/science.aay8826","volume":"370","author":"NF Darwich","year":"2020","unstructured":"Darwich, N. F. et al. Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau. Science 370, eaay8826 (2020).","journal-title":"Science"},{"key":"1879_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70427","volume":"21","author":"R Watanabe","year":"2025","unstructured":"Watanabe, R. et al. Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G. Alzheimers Dement. 21, e70427 (2025).","journal-title":"Alzheimers Dement."},{"key":"1879_CR13","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","volume":"26","author":"S Dujardin","year":"2020","unstructured":"Dujardin, S. et al. Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease. Nat. Med. 26, 1256\u20131263 (2020).","journal-title":"Nat. Med."},{"key":"1879_CR14","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jsb.2017.02.003","volume":"198","author":"S He","year":"2017","unstructured":"He, S. & Scheres, S. H. W. Helical reconstruction in RELION. J. Struct. Biol. 198, 163\u2013176 (2017).","journal-title":"J. Struct. Biol."},{"key":"1879_CR15","doi-asserted-by":"publisher","first-page":"e76494","DOI":"10.7554\/eLife.76494","volume":"11","author":"S Lovestam","year":"2022","unstructured":"Lovestam, S. et al. Assembly of recombinant tau into filaments identical to those of Alzheimer\u2019s disease and chronic traumatic encephalopathy. eLife 11, e76494 (2022).","journal-title":"eLife"},{"key":"1879_CR16","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-023-06788-w","volume":"625","author":"S Lovestam","year":"2024","unstructured":"Lovestam, S. et al. Disease-specific tau filaments assemble via polymorphic intermediates. Nature 625, 119\u2013125 (2024).","journal-title":"Nature"},{"key":"1879_CR17","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1016\/j.str.2017.10.007","volume":"25","author":"MA Nakasone","year":"2017","unstructured":"Nakasone, M. A. et al. Structural basis for the inhibitory effects of ubistatins in the ubiquitin\u2013proteasome pathway. Structure 25, 1839\u20131855 (2017).","journal-title":"Structure"},{"key":"1879_CR18","doi-asserted-by":"publisher","first-page":"10825","DOI":"10.1074\/jbc.M512786200","volume":"281","author":"D Cripps","year":"2006","unstructured":"Cripps, D. et al. Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J. Biol. Chem. 281, 10825\u201310838 (2006).","journal-title":"J. Biol. Chem."},{"key":"1879_CR19","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.molcel.2009.06.010","volume":"35","author":"N Zhang","year":"2009","unstructured":"Zhang, N. et al. Structure of the S5a:K48-linked diubiquitin complex and its interactions with Rpn13. Mol. Cell 35, 280\u2013290 (2009).","journal-title":"Mol. Cell"},{"key":"1879_CR20","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1093\/brain\/awab091","volume":"144","author":"A Tarutani","year":"2021","unstructured":"Tarutani, A. et al. Human tauopathy-derived tau strains determine the substrates recruited for templated amplification. Brain 144, 2333\u20132348 (2021).","journal-title":"Brain"},{"key":"1879_CR21","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/0896-6273(93)90063-W","volume":"10","author":"M Morishima-Kawashima","year":"1993","unstructured":"Morishima-Kawashima, M. et al. Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments. Neuron 10, 1151\u20131160 (1993).","journal-title":"Neuron"},{"key":"1879_CR22","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1073\/pnas.1502214112","volume":"112","author":"AW Fitzpatrick","year":"2015","unstructured":"Fitzpatrick, A. W., Vanacore, G. M. & Zewail, A. H. Nanomechanics and intermolecular forces of amyloid revealed by four-dimensional electron microscopy. Proc. Natl Acad. Sci. USA 112, 3380\u20133385 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1879_CR23","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/s41586-024-07680-x","volume":"631","author":"MAG Gilbert","year":"2024","unstructured":"Gilbert, M. A. G. et al. CryoET of \u03b2-amyloid and tau within postmortem Alzheimer\u2019s disease brain. Nature 631, 913\u2013919 (2024).","journal-title":"Nature"},{"key":"1879_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47066-1","volume":"15","author":"BC Creekmore","year":"2024","unstructured":"Creekmore, B. C., Kixmoeller, K., Black, B. E., Lee, E. B. & Chang, Y. W. Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling. Nat. Commun. 15, 2660 (2024).","journal-title":"Nat. Commun."},{"key":"1879_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01664-0","volume":"11","author":"ED Smith","year":"2023","unstructured":"Smith, E. D. et al. Human tauopathy strains defined by phosphorylation in R1\u2013R2 repeat domains of tau. Acta Neuropathol. Commun. 11, 172 (2023).","journal-title":"Acta Neuropathol. Commun."},{"key":"1879_CR26","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/0022-2836(87)90679-6","volume":"194","author":"S Vijay-Kumar","year":"1987","unstructured":"Vijay-Kumar, S., Bugg, C. E. & Cook, W. J. Structure of ubiquitin refined at 1.8\u2009\u00c5 resolution. J. Mol. Biol. 194, 531\u2013544 (1987).","journal-title":"J. Mol. Biol."},{"key":"1879_CR27","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"1879_CR28","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00401-017-1679-9","volume":"134","author":"EB Lee","year":"2017","unstructured":"Lee, E. B. et al. Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. Acta Neuropathol. 134, 65\u201378 (2017).","journal-title":"Acta Neuropathol."},{"key":"1879_CR29","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1107\/S205225251801463X","volume":"6","author":"J Zivanov","year":"2019","unstructured":"Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ 6, 5\u201317 (2019).","journal-title":"IUCrJ"},{"key":"1879_CR30","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","volume":"192","author":"A Rohou","year":"2015","unstructured":"Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216\u2013221 (2015).","journal-title":"J. Struct. Biol."},{"key":"1879_CR31","doi-asserted-by":"publisher","first-page":"e42166","DOI":"10.7554\/eLife.42166","volume":"7","author":"J Zivanov","year":"2018","unstructured":"Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).","journal-title":"eLife"},{"key":"1879_CR32","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1107\/S2052252520000081","volume":"7","author":"J Zivanov","year":"2020","unstructured":"Zivanov, J., Nakane, T. & Scheres, S. H. W. Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1. IUCrJ 7, 253\u2013267 (2020).","journal-title":"IUCrJ"},{"key":"1879_CR33","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","volume":"135","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24\u201335 (2013).","journal-title":"Ultramicroscopy"},{"key":"1879_CR34","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","volume":"30","author":"EF Pettersen","year":"2021","unstructured":"Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70\u201382 (2021).","journal-title":"Protein Sci."},{"key":"1879_CR35","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41586-024-07215-4","volume":"628","author":"K Jamali","year":"2024","unstructured":"Jamali, K. et al. Automated model building and protein identification in cryo-EM maps. Nature 628, 450\u2013457 (2024).","journal-title":"Nature"},{"key":"1879_CR36","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1879_CR37","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1107\/S2059798318006551","volume":"74","author":"PV Afonine","year":"2018","unstructured":"Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531\u2013544 (2018).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"1879_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2021.107826","volume":"214","author":"R Warshamanage","year":"2022","unstructured":"Warshamanage, R., Yamashita, K. & Murshudov, G. N. EMDA: a Python package for electron microscopy data analysis. J. Struct. Biol. 214, 107826 (2022).","journal-title":"J. Struct. Biol."}],"container-title":["Nature Structural & Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-026-01879-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-026-01879-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-026-01879-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:22:34Z","timestamp":1792106554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-026-01879-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["1879"],"URL":"https:\/\/doi.org\/10.1038\/s41594-026-01879-4","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"17 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the version of the article initially published, the first row of \"Table\n                      \n                      (continued)\" was incorrect in the PDF version of the article and should have read \u201cubiB-VT Case 1\u201d (the HTML version of the table was correct). Additionally, in the Extended Data Fig.\n                      \n                      legend, PDB 80T9 was cited as ref. 7 but should have been ref. 4. These corrections have been made to the HTML and PDF versions of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"E.B.L. has received consulting fees from Eli Lilly unrelated to this study. All other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}