Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)
Abstract Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, sugges...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43822-x |
| _version_ | 1797274135049535488 |
|---|---|
| author | Benedikt Frieg Mookyoung Han Karin Giller Christian Dienemann Dietmar Riedel Stefan Becker Loren B. Andreas Christian Griesinger Gunnar F. Schröder |
| author_facet | Benedikt Frieg Mookyoung Han Karin Giller Christian Dienemann Dietmar Riedel Stefan Becker Loren B. Andreas Christian Griesinger Gunnar F. Schröder |
| author_sort | Benedikt Frieg |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils, as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions. |
| first_indexed | 2024-03-07T14:54:02Z |
| format | Article |
| id | doaj.art-f12a70bcf0274200ae54e24f2672d1af |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:54:02Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f12a70bcf0274200ae54e24f2672d1af2024-03-05T19:34:26ZengNature PortfolioNature Communications2041-17232024-02-0115111110.1038/s41467-023-43822-xCryo-EM structures of lipidic fibrils of amyloid-β (1-40)Benedikt Frieg0Mookyoung Han1Karin Giller2Christian Dienemann3Dietmar Riedel4Stefan Becker5Loren B. Andreas6Christian Griesinger7Gunnar F. Schröder8Institute of Biological Information Processing (IBI-7: Structural Biochemistry) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum JülichDepartment of NMR-Based Structural Biology, Max Planck Institute for Multidisciplinary SciencesDepartment of NMR-Based Structural Biology, Max Planck Institute for Multidisciplinary SciencesDepartment of Molecular Biology, Max Planck Institute for Multidisciplinary SciencesLaboratory of Electron Microscopy, Max-Planck-Institute for Multidisciplinary SciencesDepartment of NMR-Based Structural Biology, Max Planck Institute for Multidisciplinary SciencesDepartment of NMR-Based Structural Biology, Max Planck Institute for Multidisciplinary SciencesDepartment of NMR-Based Structural Biology, Max Planck Institute for Multidisciplinary SciencesInstitute of Biological Information Processing (IBI-7: Structural Biochemistry) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum JülichAbstract Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils, as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.https://doi.org/10.1038/s41467-023-43822-x |
| spellingShingle | Benedikt Frieg Mookyoung Han Karin Giller Christian Dienemann Dietmar Riedel Stefan Becker Loren B. Andreas Christian Griesinger Gunnar F. Schröder Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) Nature Communications |
| title | Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) |
| title_full | Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) |
| title_fullStr | Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) |
| title_full_unstemmed | Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) |
| title_short | Cryo-EM structures of lipidic fibrils of amyloid-β (1-40) |
| title_sort | cryo em structures of lipidic fibrils of amyloid β 1 40 |
| url | https://doi.org/10.1038/s41467-023-43822-x |
| work_keys_str_mv | AT benediktfrieg cryoemstructuresoflipidicfibrilsofamyloidb140 AT mookyounghan cryoemstructuresoflipidicfibrilsofamyloidb140 AT karingiller cryoemstructuresoflipidicfibrilsofamyloidb140 AT christiandienemann cryoemstructuresoflipidicfibrilsofamyloidb140 AT dietmarriedel cryoemstructuresoflipidicfibrilsofamyloidb140 AT stefanbecker cryoemstructuresoflipidicfibrilsofamyloidb140 AT lorenbandreas cryoemstructuresoflipidicfibrilsofamyloidb140 AT christiangriesinger cryoemstructuresoflipidicfibrilsofamyloidb140 AT gunnarfschroder cryoemstructuresoflipidicfibrilsofamyloidb140 |