Application study of infrared free-electron lasers towards the development of amyloidosis therapy
Amyloidosis is known to be caused by the deposition of amyloid fibrils into various biological tissues; effective treatments for the disease are little established today. An infrared free-electron laser (IR-FEL) is an accelerator-based picosecond-pulse laser having tunable infrared wavelengths. In t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2022-09-01
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| Series: | Journal of Synchrotron Radiation |
| Subjects: | |
| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S1600577522007330 |
| _version_ | 1811209599520342016 |
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| author | Mikiko Jindo Kazuhiro Nakamura Hisashi Okumura Koichi Tsukiyama Takayasu Kawasaki |
| author_facet | Mikiko Jindo Kazuhiro Nakamura Hisashi Okumura Koichi Tsukiyama Takayasu Kawasaki |
| author_sort | Mikiko Jindo |
| collection | DOAJ |
| description | Amyloidosis is known to be caused by the deposition of amyloid fibrils into various biological tissues; effective treatments for the disease are little established today. 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 β2-microglobulin (β2M) with the aim of applying IR-FELs to amyloidosis therapy. Infrared microspectroscopy (IRM) and scanning electron microscopy showed that a fibril of β2M peptide was clearly dissociated by IR-FEL at 6.1 µm (amide I) accompanied by a decrease of the β-sheet and an increase of the α-helix. No dissociative process was recognized at 6.5 µm (amide II) as well as at 5.0 µm (non-specific wavelength). Equilibrium molecular dynamics simulations indicated that the α-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 β-sheet is dissociated by amide I specific irradiation. This result implies that N4 plays a key role for recombination of hydrogen bonds in the dissociation of the β2M fibril. In addition, the β-sheet was disrupted at temperatures higher than 340 K while the α-helix did not appear even though the fibril was heated up to 363 K as revealed by IRM. The current study gives solid evidence for the laser-mediated conversion from β-sheet to α-helix in amyloid fibrils at the molecular level. |
| first_indexed | 2024-04-12T04:41:28Z |
| format | Article |
| id | doaj.art-9c749a2b15324e78a01820e8d8d94cfa |
| institution | Directory Open Access Journal |
| issn | 1600-5775 |
| language | English |
| last_indexed | 2024-04-12T04:41:28Z |
| publishDate | 2022-09-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | Journal of Synchrotron Radiation |
| spelling | doaj.art-9c749a2b15324e78a01820e8d8d94cfa2022-12-22T03:47:36ZengInternational Union of CrystallographyJournal of Synchrotron Radiation1600-57752022-09-012951133114010.1107/S1600577522007330yi5122Application study of infrared free-electron lasers towards the development of amyloidosis therapyMikiko Jindo0Kazuhiro Nakamura1Hisashi Okumura2Koichi Tsukiyama3Takayasu Kawasaki4Department of Chemistry, Faculty of Science Division I, Tokyo University of Science, 1–3 Kagurazaka, Tokyo 184-8501, JapanDepartment of Laboratory Sciences, Gunma University, Graduate School of Health Sciences, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, JapanExploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, JapanDepartment of Chemistry, Faculty of Science Division I, Tokyo University of Science, 1–3 Kagurazaka, Tokyo 184-8501, JapanIR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanAmyloidosis is known to be caused by the deposition of amyloid fibrils into various biological tissues; effective treatments for the disease are little established today. 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 β2-microglobulin (β2M) with the aim of applying IR-FELs to amyloidosis therapy. Infrared microspectroscopy (IRM) and scanning electron microscopy showed that a fibril of β2M peptide was clearly dissociated by IR-FEL at 6.1 µm (amide I) accompanied by a decrease of the β-sheet and an increase of the α-helix. No dissociative process was recognized at 6.5 µm (amide II) as well as at 5.0 µm (non-specific wavelength). Equilibrium molecular dynamics simulations indicated that the α-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 β-sheet is dissociated by amide I specific irradiation. This result implies that N4 plays a key role for recombination of hydrogen bonds in the dissociation of the β2M fibril. In addition, the β-sheet was disrupted at temperatures higher than 340 K while the α-helix did not appear even though the fibril was heated up to 363 K as revealed by IRM. The current study gives solid evidence for the laser-mediated conversion from β-sheet to α-helix in amyloid fibrils at the molecular level.http://scripts.iucr.org/cgi-bin/paper?S1600577522007330infrared free-electron laseramyloidosisamyloid fibrilβ2-microglobulin |
| spellingShingle | Mikiko Jindo Kazuhiro Nakamura Hisashi Okumura Koichi Tsukiyama Takayasu Kawasaki Application study of infrared free-electron lasers towards the development of amyloidosis therapy Journal of Synchrotron Radiation infrared free-electron laser amyloidosis amyloid fibril β2-microglobulin |
| title | Application study of infrared free-electron lasers towards the development of amyloidosis therapy |
| title_full | Application study of infrared free-electron lasers towards the development of amyloidosis therapy |
| title_fullStr | Application study of infrared free-electron lasers towards the development of amyloidosis therapy |
| title_full_unstemmed | Application study of infrared free-electron lasers towards the development of amyloidosis therapy |
| title_short | Application study of infrared free-electron lasers towards the development of amyloidosis therapy |
| title_sort | application study of infrared free electron lasers towards the development of amyloidosis therapy |
| topic | infrared free-electron laser amyloidosis amyloid fibril β2-microglobulin |
| url | http://scripts.iucr.org/cgi-bin/paper?S1600577522007330 |
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