{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:43:44Z","timestamp":1791877424175,"version":"4.3.4"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Frontotemporal dementia (FTD) and Alzheimer\u2019s disease (AD) are the most common forms of early-onset dementia. Unlike AD, FTD begins with behavioral changes before the development of cognitive impairment. Dominantly inherited mutations in <jats:italic>MAPT<\/jats:italic>, the microtubule-associated protein tau gene, give rise to cases of FTD and parkinsonism linked to chromosome 17. These individuals develop abundant filamentous tau inclusions in brain cells in the absence of \u03b2-amyloid deposits. Here, we used cryo-electron microscopy to determine the structures of tau filaments from the brains of human <jats:italic>MAPT<\/jats:italic> mutants V337M and R406W. Both amino acid substitutions gave rise to tau filaments with the Alzheimer fold, which consisted of paired helical filaments in all V337M and R406W cases and of straight filaments in two V337M cases. We also identified another assembly of the Alzheimer fold into triple tau filaments in a V337M case. Filaments assembled from recombinant tau (297\u2013391) with substitution V337M had the Alzheimer fold and showed an increased rate of assembly.<\/jats:p>","DOI":"10.1038\/s41594-025-01498-5","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T05:04:25Z","timestamp":1741151065000},"page":"1297-1304","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W"],"prefix":"10.1038","volume":"32","author":[{"given":"Chao","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"L\u00f6vestam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey G.","family":"Murzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-6384","authenticated-orcid":false,"given":"Sew","family":"Peak-Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Franco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Bogdani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Latimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill R.","family":"Murrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W.","family":"Cullinane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Bird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-8019","authenticated-orcid":false,"given":"Bernardino","family":"Ghetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-6540","authenticated-orcid":false,"given":"Sjors H. W.","family":"Scheres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7886","authenticated-orcid":false,"given":"Michel","family":"Goedert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"1498_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","volume":"3","author":"M Goedert","year":"1989","unstructured":"Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D. & Crowther, R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease. Neuron 3, 519\u2013526 (1989).","journal-title":"Neuron"},{"key":"1498_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang, Y. & Mandelkow, E. Tau in physiology and pathology. Nat. Rev. Neurosci. 17, 5\u201321 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"1498_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/cm.21812","volume":"81","author":"M Goedert","year":"2024","unstructured":"Goedert, M., Crowther, R. A., Scheres, S. H. W. & Spillantini, M. G. Tau and neurodegeneration. Cytoskeleton 81, 95\u2013102 (2024).","journal-title":"Cytoskeleton"},{"key":"1498_CR4","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":"1498_CR5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s00401-023-02598-6","volume":"146","author":"M Schweighauser","year":"2023","unstructured":"Schweighauser, M. et al. Mutation \u0394K281 in MAPT causes Pick\u2019s disease. Acta Neuropathol. 146, 211\u2013226 (2023).","journal-title":"Acta Neuropathol."},{"key":"1498_CR6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41586-021-03911-7","volume":"598","author":"Y Shi","year":"2021","unstructured":"Shi, Y. et al. Structure-based classification of tauopathies. Nature 598, 359\u2013363 (2021).","journal-title":"Nature"},{"key":"1498_CR7","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41586-022-04650-z","volume":"605","author":"M Schweighauser","year":"2022","unstructured":"Schweighauser, M. et al. Age-dependent formation of TMEM106B amyloid filaments in human brains. Nature 605, 310\u2013314 (2022).","journal-title":"Nature"},{"key":"1498_CR8","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/j.cell.2022.02.026","volume":"185","author":"A Chang","year":"2022","unstructured":"Chang, A. et al. Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases. Cell 185, 1346\u20131355 (2022).","journal-title":"Cell"},{"key":"1498_CR9","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s00401-023-02563-3","volume":"145","author":"MR Hoq","year":"2023","unstructured":"Hoq, M. R. et al. Cross-\u03b2 helical filaments of tau and TMEM106B in gray and white matter of multiple system tauopathy with presenile dementia. Acta Neuropathol. 145, 707\u2013710 (2023).","journal-title":"Acta Neuropathol."},{"key":"1498_CR10","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":"1498_CR11","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":"1498_CR12","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00401-021-02336-w","volume":"142","author":"GI Hallinan","year":"2021","unstructured":"Hallinan, G. I. et al. Structure of tau filaments in prion protein amyloidoses. Acta Neuropathol. 142, 227\u2013241 (2021).","journal-title":"Acta Neuropathol."},{"key":"1498_CR13","doi-asserted-by":"publisher","first-page":"74","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":"1498_CR14","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\u2013dementia complex adopt the CTE fold. Proc. Natl Acad. Sci. USA 120, e2306767120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1498_CR15","doi-asserted-by":"publisher","first-page":"86","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":"1498_CR16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76494","volume":"11","author":"S L\u00f6vestam","year":"2022","unstructured":"L\u00f6vestam, 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":"1498_CR17","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1212\/WNL.42.1.120","volume":"42","author":"SM Sumi","year":"1992","unstructured":"Sumi, S. M., Bird, T. D., Nochlin, D. & Raskind, M. A. Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. Neurology 42, 120\u2013127 (1992).","journal-title":"Neurology"},{"key":"1498_CR18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s004010050487","volume":"92","author":"MG Spillantini","year":"1996","unstructured":"Spillantini, M. G., Crowther, R. A. & Goedert, M. Comparison of the neurofibrillary pathology in Alzheimer\u2019s disease and familial presenile dementia with tangles. Acta Neuropathol. 92, 42\u201348 (1996).","journal-title":"Acta Neuropathol."},{"key":"1498_CR19","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1750-3639.1998.tb00162.x","volume":"8","author":"MG Spillantini","year":"1998","unstructured":"Spillantini, M. G., Bird, T. D. & Ghetti, B. Frontotemporal dementia and parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol. 8, 387\u2013402 (1998).","journal-title":"Brain Pathol."},{"key":"1498_CR20","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/ana.410430617","volume":"43","author":"P Poorkaj","year":"1998","unstructured":"Poorkaj, P. et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815\u2013825 (1998).","journal-title":"Ann. Neurol."},{"key":"1498_CR21","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1212\/WNL.0000000000003636","volume":"88","author":"S Spina","year":"2017","unstructured":"Spina, S. et al. Frontotemporal dementia with the V337M MAPT mutation. Neurology 88, 758\u2013766 (2017).","journal-title":"Neurology"},{"key":"1498_CR22","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/ana.410420406","volume":"42","author":"LA Reed","year":"1997","unstructured":"Reed, L. A. et al. Autosomal dominant dementia with widespread neurofibrillary tangles. Ann. Neurol. 42, 564\u2013572 (1997).","journal-title":"Ann. Neurol."},{"key":"1498_CR23","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/31508","volume":"393","author":"M Hutton","year":"1998","unstructured":"Hutton, M. et al. Association of missense and 5\u2032-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702\u2013705 (1998).","journal-title":"Nature"},{"key":"1498_CR24","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/1531-8249(199910)46:4<617::AID-ANA10>3.0.CO;2-I","volume":"46","author":"JC Van Swieten","year":"1999","unstructured":"Van Swieten, J. C. et al. Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann. Neurol. 46, 617\u2013626 (1999).","journal-title":"Ann. Neurol."},{"key":"1498_CR25","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1212\/WNL.58.5.811","volume":"58","author":"Y Saito","year":"2002","unstructured":"Saito, Y. et al. Early-onset, rapidly progressive familial tauopathy with R406W mutation. Neurology 58, 811\u2013813 (2002).","journal-title":"Neurology"},{"key":"1498_CR26","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/j.1468-1331.2008.02069.x","volume":"15","author":"SG Lindquist","year":"2008","unstructured":"Lindquist, S. G. et al. Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by MAPT R406W mutation. Eur. J. Neurol. 15, 377\u2013385 (2008).","journal-title":"Eur. J. Neurol."},{"key":"1498_CR27","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1093\/brain\/aww163","volume":"139","author":"R Smith","year":"2016","unstructured":"Smith, R. et al. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers. Brain 139, 2372\u20132379 (2016).","journal-title":"Brain"},{"key":"1498_CR28","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13195-017-0330-2","volume":"10","author":"E Ygland","year":"2018","unstructured":"Ygland, E. et al. Slow progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review. Alzheimers Res. Ther. 10, 2 (2018).","journal-title":"Alzheimers Res. Ther."},{"key":"1498_CR29","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1212\/WNL.48.4.949","volume":"48","author":"TD Bird","year":"1997","unstructured":"Bird, T. D. et al. Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD. Neurology 48, 949\u2013954 (1997).","journal-title":"Neurology"},{"key":"1498_CR30","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1159\/000077158","volume":"17","author":"J Ostojic","year":"2004","unstructured":"Ostojic, J. et al. The tau R406W mutation causes progressive dementia with bitemporal atrophy. Dement. Geriatr. Cogn. Disord. 17, 298\u2013301 (2004).","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"1498_CR31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/acn3.51249","volume":"8","author":"SA Chu","year":"2021","unstructured":"Chu, S. A. et al. Brain volumetric deficits in MAPT mutation carriers: a multisite study. Ann. Clin. Transl. Neurol. 8, 95\u2013110 (2021).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"1498_CR32","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0002-9440(10)63979-X","volume":"158","author":"T Miyasaka","year":"2001","unstructured":"Miyasaka, T. et al. Molecular analysis of mutant and wild-type tau deposited in the brain affected by the FTDP-17 R406W mutation. Am. J. Pathol. 158, 373\u2013379 (2001).","journal-title":"Am. J. Pathol."},{"key":"1498_CR33","doi-asserted-by":"publisher","first-page":"e947","DOI":"10.1212\/WNL.0000000000005117","volume":"90","author":"DT Jones","year":"2018","unstructured":"Jones, D. T. et al. In vivo 18F-AV-1451 tau PET signal in MAPT mutation carriers by expected tau isoforms. Neurology 90, e947\u2013e954 (2018).","journal-title":"Neurology"},{"key":"1498_CR34","doi-asserted-by":"publisher","first-page":"e1017","DOI":"10.1212\/WNL.0000000000012448","volume":"97","author":"EE Wolters","year":"2021","unstructured":"Wolters, E. E. et al. [18F] Flortaucipir PET across various MAPT mutations in presymptomatic and symptomatic carriers. Neurology 97, e1017\u2013e1030 (2021).","journal-title":"Neurology"},{"key":"1498_CR35","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.jalz.2019.09.079","volume":"16","author":"VJ Lowe","year":"2020","unstructured":"Lowe, V. J. et al. Tau-positron emission tomography correlates with neuropathology findings. Alzheimers Dement. 16, 561\u2013571 (2020).","journal-title":"Alzheimers Dement."},{"key":"1498_CR36","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s40478-018-0608-z","volume":"6","author":"SL Risacher","year":"2018","unstructured":"Risacher, S. L. et al. Detection of tau in Gerstmann\u2013Str\u00e4ussler\u2013Scheinker disease (PRNP F198S) by [18F] flortaucipir PET. Acta Neuropathol. Commun. 6, 114 (2018).","journal-title":"Acta Neuropathol. Commun."},{"key":"1498_CR37","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1038\/s41591-023-02443-z","volume":"29","author":"K Horie","year":"2023","unstructured":"Horie, K. et al. CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer\u2019s disease. Nat. Med. 29, 1954\u20131963 (2023).","journal-title":"Nat. Med."},{"key":"1498_CR38","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1002\/alz.12321","volume":"17","author":"CM Moloney","year":"2021","unstructured":"Moloney, C. M., Lowe, V. J. & Murray, M. E. Visualization of neurofibrillary tangle maturity in Alzheimer\u2019s disease: a clinicopathologic perspective for biomarker research. Alzheimers Dement. 17, 1554\u20131574 (2021).","journal-title":"Alzheimers Dement."},{"key":"1498_CR39","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s40478-021-01189-4","volume":"9","author":"JD Cherry","year":"2021","unstructured":"Cherry, J. D. et al. Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer\u2019s disease. Acta Neuropathol. Commun. 9, 86 (2021).","journal-title":"Acta Neuropathol. Commun."},{"key":"1498_CR40","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/BF00309621","volume":"89","author":"P Cras","year":"1995","unstructured":"Cras, P. et al. Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease. Acta Neuropathol. 89, 291\u2013295 (1995).","journal-title":"Acta Neuropathol."},{"key":"1498_CR41","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-020-2043-0","volume":"580","author":"W Zhang","year":"2020","unstructured":"Zhang, W. et al. Novel tau filament fold in corticobasal degeneration. Nature 580, 283\u2013287 (2020).","journal-title":"Nature"},{"key":"1498_CR42","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0014-5793(98)01217-4","volume":"437","author":"M Hasegawa","year":"1998","unstructured":"Hasegawa, M., Smith, M. J. & Goedert, M. Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett. 437, 207\u2013210 (1998).","journal-title":"FEBS Lett."},{"key":"1498_CR43","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S0006-8993(99)02124-1","volume":"853","author":"M De Ture","year":"2000","unstructured":"De Ture, M. et al. Missense tau mutations identified in FTDP-17 have a small effect on tau\u2013microtubule interactions. Brain Res. 853, 5\u201314 (2000).","journal-title":"Brain Res."},{"key":"1498_CR44","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/S0014-5793(99)00508-6","volume":"450","author":"M Goedert","year":"1999","unstructured":"Goedert, M., Jakes, R. & Crowther, R. A. Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett. 450, 306\u2013311 (1999).","journal-title":"FEBS Lett."},{"key":"1498_CR45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43584","volume":"8","author":"W Zhang","year":"2019","unstructured":"Zhang, W. et al. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases. eLife 8, e43584 (2019).","journal-title":"eLife"},{"key":"1498_CR46","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1093\/brain\/awm280","volume":"131","author":"S Spina","year":"2008","unstructured":"Spina, S. et al. The tauopathy associated with mutation +3 in intron 10 of tau: characterization of the MSTD family. Brain 131, 72\u201389 (2008).","journal-title":"Brain"},{"key":"1498_CR47","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40478-018-0532-2","volume":"6","author":"A Tarutani","year":"2018","unstructured":"Tarutani, A., Arai, T., Murayama, S., Hisanaga, S. I. & Hasegawa, M. Potent prion-like behaviours of pathogenic \u03b1-synuclein and evaluation of inactivation methods. Acta Neuropathol. Commun. 6, 29 (2018).","journal-title":"Acta Neuropathol. Commun."},{"key":"1498_CR48","first-page":"27459","volume":"6","author":"J Garc\u00eda-Nafr\u00eda","year":"2016","unstructured":"Garc\u00eda-Nafr\u00eda, J., Watson, J. F. & Greger, I. H. IVA cloning: a single-tube universal cloning system exploiting bacterial in vivo assembly. Sci. Adv. 6, 27459 (2016).","journal-title":"Sci. Adv."},{"key":"1498_CR49","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.pep.2005.01.016","volume":"41","author":"FW Studier","year":"2005","unstructured":"Studier, F. W. Protein production by auto-induction in high density shaking cultures. Protein Expr. Purif. 41, 207\u2013234 (2005).","journal-title":"Protein Expr. Purif."},{"key":"1498_CR50","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1107\/S205225252000929X","volume":"7","author":"H Guo","year":"2020","unstructured":"Guo, H. et al. Electron-event representation data enable efficient cryo-EM file storage with full preservation of spatial and temporal resolution. IUCrJ 7, 860\u2013869 (2020).","journal-title":"IUCrJ"},{"key":"1498_CR51","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jsb.2017.02.003","volume":"193","author":"S He","year":"2017","unstructured":"He, S. & Scheres, S. H. W. Helical reconstruction in RELION. J. Struct. Biol. 193, 163\u2013176 (2017).","journal-title":"J. Struct. Biol."},{"key":"1498_CR52","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.1042\/BCJ20210708","volume":"478","author":"D Kimanius","year":"2021","unstructured":"Kimanius, D., Long, K. L., Sharov, G., Nakane, T. & Scheres, S. H. W. New tools for automated cryo-EM single-particle analysis in RELION-4.0. Biochem. J. 478, 4169\u20134185 (2021).","journal-title":"Biochem. J."},{"key":"1498_CR53","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":"1498_CR54","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":"1498_CR55","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":"1498_CR56","doi-asserted-by":"publisher","first-page":"e83724","DOI":"10.7554\/eLife.83724","volume":"11","author":"J Zivanov","year":"2022","unstructured":"Zivanov, J. et al. A Bayesian approach to single-particle electron-tomography in RELION-4.0. eLife 11, e83724 (2022).","journal-title":"eLife"},{"key":"1498_CR57","doi-asserted-by":"publisher","first-page":"8453","DOI":"10.1038\/nmeth.2115","volume":"9","author":"SHW Scheres","year":"2012","unstructured":"Scheres, S. H. W. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9, 8453\u20138454 (2012).","journal-title":"Nat. Methods"},{"key":"1498_CR58","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":"1498_CR59","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1107\/S2059798318002425","volume":"74","author":"TI Croll","year":"2018","unstructured":"Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron density map. Acta Crystallogr. D Struct. Biol. 74, 519\u2013530 (2018).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"1498_CR60","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1107\/S2059798321009475","volume":"77","author":"K Yamashita","year":"2021","unstructured":"Yamashita, K., Palmer, C. M., Burnley, T. & Murshudov, G. N. Cryo-EM single particle structure refinement and map calculation using Servalcat. Acta Crystallogr. D Struct. Biol. 77, 1282\u20131291 (2021).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"1498_CR61","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240\u2013255 (1997).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1498_CR62","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1107\/S0907444911001314","volume":"67","author":"GN Murshudov","year":"2011","unstructured":"Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 255\u2013267 (2011).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1498_CR63","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 2\u201321 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1498_CR64","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","volume":"30","author":"EF Pettersen","year":"2011","unstructured":"Pettersen, E. F. et al. Chimera X: structure visualization for researchers, editors and developers. Protein Sci. 30, 70\u201382 (2011).","journal-title":"Protein Sci."}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-025-01498-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-025-01498-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-025-01498-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T07:25:39Z","timestamp":1757143539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-025-01498-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":64,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["1498"],"URL":"https:\/\/doi.org\/10.1038\/s41594-025-01498-5","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"29 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}