{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:51:09Z","timestamp":1790196669801,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Ubiquitin and its polymeric forms are conjugated to intracellular proteins to regulate diverse intracellular processes. Intriguingly, polyubiquitin has also been identified as a component of pathological protein aggregates associated with Alzheimer\u2019s disease and other neurodegenerative disorders. We recently found that polyubiquitin can form amyloid-like fibrils, and that these fibrillar aggregates can be degraded by macroautophagy. Although the structural properties appear to function in recognition of the fibrils, no structural information on polyubiquitin fibrils has been reported so far. Here, we identify the core of M1-linked diubiquitin fibrils from hydrogen-deuterium exchange experiments using solution nuclear magnetic resonance (NMR) spectroscopy. Intriguingly, intrinsically flexible regions became highly solvent-protected in the fibril structure. These results indicate that polyubiquitin fibrils are formed by inter-molecular interactions between relatively flexible structural components, including the loops and edges of secondary structure elements.<\/jats:p>","DOI":"10.3390\/polym10030240","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T14:18:08Z","timestamp":1519741088000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hydrogen-Deuterium Exchange Profiles of Polyubiquitin Fibrils"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7672-2136","authenticated-orcid":false,"given":"Daichi","family":"Morimoto","sequence":"first","affiliation":[{"name":"Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-6401","authenticated-orcid":false,"given":"Erik","family":"Walinda","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-7743","authenticated-orcid":false,"given":"Kenji","family":"Sugase","sequence":"additional","affiliation":[{"name":"Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-biochem-060310-170328","article-title":"The ubiquitin code","volume":"81","author":"Komander","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1126\/science.3029875","article-title":"Ubiquitin is a component of paired helical filaments in Alzheimer\u2019s disease","volume":"235","author":"Mori","year":"1987","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/337687a0","article-title":"Brain diseases. Ubiquitous variations in nerves","volume":"337","author":"Gallo","year":"1989","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6116","DOI":"10.1038\/ncomms7116","article-title":"The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates","volume":"6","author":"Morimoto","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24944","DOI":"10.1074\/jbc.M114.580357","article-title":"Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway","volume":"289","author":"Kageyama","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1515\/bmc-2016-0009","article-title":"The evolving world of ubiquitin: Transformed polyubiquitin chains","volume":"7","author":"Morimoto","year":"2016","journal-title":"Biomol. Concepts"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13597","DOI":"10.1073\/pnas.250288897","article-title":"A\u03b2 amyloid fibrils possess a core structure highly resistant to hydrogen exchange","volume":"97","author":"Kheterpal","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39453","DOI":"10.1038\/srep39453","article-title":"Ubiquitylation directly induces fold destabilization of proteins","volume":"6","author":"Morimoto","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1107\/S1744309110018804","article-title":"Purification, crystallization and preliminary crystallographic studies of Lys48-linked polyubiquitin chains","volume":"66","author":"Morimoto","year":"2010","journal-title":"Acta. Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/jmra.1995.1047","article-title":"Water suppression that works. Excitation sculpting using arbitrary wave-forms and pulsed-field gradients","volume":"112","author":"Hwang","year":"1995","journal-title":"J. Magn. Reson. Ser. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1006\/jmrb.1993.1033","article-title":"HNCACB, a high-sensitivity 3D NMR experiment to correlate amide-proton and nitrogen resonances with the alpha- and beta-carbon resonances in proteins","volume":"101","author":"Wittekind","year":"1993","journal-title":"J. Magn. Reson. Ser. B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF00178261","article-title":"Amino acid type determination in the sequential assignment procedure of uniformly 13C\/15N-enriched proteins","volume":"3","author":"Grzesiek","year":"1993","journal-title":"J. Biomol. NMR"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10858-014-9890-7","article-title":"Easy and unambiguous sequential assignments of intrinsically disordered proteins by correlating the backbone 15N or 13C\u2019 chemical shifts of multiple contiguous residues in highly resolved 3D spectra","volume":"61","author":"Yoshimura","year":"2015","journal-title":"J. Biomol. NMR"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1351\/pac199870010117","article-title":"Recommendations for the presentation of NMR structures of proteins and nucleic acids\u2014(IUPAC Recommendations 1998)","volume":"70","author":"Markley","year":"1998","journal-title":"Pure. Appl. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: A multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J. Biomol. NMR"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/prot.20449","article-title":"The CCPN data model for NMR spectroscopy: Development of a software pipeline","volume":"59","author":"Vranken","year":"2005","journal-title":"Proteins"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10858-013-9747-5","article-title":"Fast and accurate fitting of relaxation dispersion data using the flexible software package GLOVE","volume":"56","author":"Sugase","year":"2013","journal-title":"J. Biomol. NMR"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nsb792","article-title":"Mapping the core of the \u03b22-microglobulin amyloid fibril by H\/D exchange","volume":"9","author":"Hoshino","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/embor.2009.55","article-title":"Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains","volume":"10","author":"Komander","year":"2009","journal-title":"EMBO. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7286","DOI":"10.1021\/acs.analchem.7b01816","article-title":"High-sensitivity Rheo-NMR spectroscopy for protein studies","volume":"89","author":"Morimoto","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31864","DOI":"10.1074\/jbc.M111.259630","article-title":"Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its interaction with ubiquitin","volume":"286","author":"Isogai","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13890","DOI":"10.1074\/jbc.M114.555441","article-title":"Solution structure of the ubiquitin-associated (UBA) domain of human autophagy receptor NBR1 and its interaction with ubiquitin and polyubiquitin","volume":"289","author":"Walinda","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nchembio.131","article-title":"Amyloid formation by globular proteins under native conditions","volume":"5","author":"Chiti","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nsb935","article-title":"Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS","volume":"10","author":"Elam","year":"2003","journal-title":"Nat. Struct. Biol."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/10\/3\/240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:56:41Z","timestamp":1760194601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/10\/3\/240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,27]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["polym10030240"],"URL":"https:\/\/doi.org\/10.3390\/polym10030240","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,27]]}}}