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An infrared free-electron laser (IR-FEL) is an accelerator-based picosecond-pulse laser having tunable infrared wavelengths. In the current study, the irradiation effect of an IR-FEL was tested on an 11-residue peptide (NFLNCYVSGFH) fibril from \u03b22-microglobulin (\u03b22M) with the aim of applying IR-FELs to amyloidosis therapy. Infrared microspectroscopy (IRM) and scanning electron microscopy showed that a fibril of \u03b22M peptide was clearly dissociated by IR-FEL at 6.1\u2005\u00b5m (amide\u2005I) accompanied by a decrease of the \u03b2-sheet and an increase of the \u03b1-helix. No dissociative process was recognized at 6.5\u2005\u00b5m (amide\u2005II) as well as at 5.0\u2005\u00b5m (non-specific wavelength). Equilibrium molecular dynamics simulations indicated that the \u03b1-helix can exist stably and the probability of forming interchain hydrogen bonds associated with the internal asparagine residue (N4) is notably reduced compared with other amino acids after the \u03b2-sheet is dissociated by amide\u2005I specific irradiation. This result implies that N4 plays a key role for recombination of hydrogen bonds in the dissociation of the \u03b22M fibril. In addition, the \u03b2-sheet was disrupted at temperatures higher than 340\u2005K while the \u03b1-helix did not appear even though the fibril was heated up to 363\u2005K as revealed by IRM. The current study gives solid evidence for the laser-mediated conversion from \u03b2-sheet to \u03b1-helix in amyloid fibrils at the molecular level.<\/jats:p>","DOI":"10.1107\/s1600577522007330","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T10:48:31Z","timestamp":1660301311000},"page":"1133-1140","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":7,"title":["Application study of infrared free-electron lasers towards the development of amyloidosis therapy"],"prefix":"10.1107","volume":"29","author":[{"given":"Mikiko","family":"Jindo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05sj3n476","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Chemistry, Faculty of Science Division I"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nakamura","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046fm7598","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Laboratory Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-5604","authenticated-orcid":true,"given":"Hisashi","family":"Okumura","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055n47h92","id-type":"ROR","asserted-by":"publisher"}],"department":["Exploratory Research Center on Life and Living Systems (ExCELLS)"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-5053","authenticated-orcid":true,"given":"Koichi","family":"Tsukiyama","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05sj3n476","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Chemistry, Faculty of Science Division I"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayasu","family":"Kawasaki","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05sj3n476","id-type":"ROR","asserted-by":"publisher"}],"department":["IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"yi5122_bb1","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1021\/acs.jpca.9b11811","volume":"124","author":"Andersson","year":"2020","journal-title":"J. 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