Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis
Abstract Systemic ALys amyloidosis is a debilitating protein misfolding disease that arises from the formation of amyloid fibrils from C-type lysozyme. We here present a 2.8 Å cryo-electron microscopy structure of an amyloid fibril, which was isolated from the abdominal fat tissue of a patient who e...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54091-7 |
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| author | Sara Karimi-Farsijani Kartikay Sharma Marijana Ugrina Lukas Kuhn Peter Benedikt Pfeiffer Christian Haupt Sebastian Wiese Ute Hegenbart Stefan O. Schönland Nadine Schwierz Matthias Schmidt Marcus Fändrich |
| author_facet | Sara Karimi-Farsijani Kartikay Sharma Marijana Ugrina Lukas Kuhn Peter Benedikt Pfeiffer Christian Haupt Sebastian Wiese Ute Hegenbart Stefan O. Schönland Nadine Schwierz Matthias Schmidt Marcus Fändrich |
| author_sort | Sara Karimi-Farsijani |
| collection | DOAJ |
| description | Abstract Systemic ALys amyloidosis is a debilitating protein misfolding disease that arises from the formation of amyloid fibrils from C-type lysozyme. We here present a 2.8 Å cryo-electron microscopy structure of an amyloid fibril, which was isolated from the abdominal fat tissue of a patient who expressed the D87G variant of human lysozyme. We find that the fibril possesses a stable core that is formed by all 130 residues of the fibril precursor protein. There are four disulfide bonds in each fibril protein that connect the same residues as in the globularly folded protein. As the conformation of lysozyme in the fibril is otherwise fundamentally different from native lysozyme, our data provide a structural rationale for the need of protein unfolding in the development of systemic ALys amyloidosis. |
| format | Article |
| id | doaj-art-f810210754504cdca3221e85b66b7ea6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f810210754504cdca3221e85b66b7ea62024-11-10T12:33:23ZengNature PortfolioNature Communications2041-17232024-11-011511910.1038/s41467-024-54091-7Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosisSara Karimi-Farsijani0Kartikay Sharma1Marijana Ugrina2Lukas Kuhn3Peter Benedikt Pfeiffer4Christian Haupt5Sebastian Wiese6Ute Hegenbart7Stefan O. Schönland8Nadine Schwierz9Matthias Schmidt10Marcus Fändrich11Institute of Protein Biochemistry, Ulm UniversityInstitute of Protein Biochemistry, Ulm UniversityInstitute of Physics, University of AugsburgInstitute of Protein Biochemistry, Ulm UniversityInstitute of Protein Biochemistry, Ulm UniversityInstitute of Protein Biochemistry, Ulm UniversityCore Unit Mass Spectrometry and Proteomics, Medical Faculty, Ulm UniversityMedical Department V, Amyloidosis Center, Heidelberg University HospitalMedical Department V, Amyloidosis Center, Heidelberg University HospitalInstitute of Physics, University of AugsburgInstitute of Protein Biochemistry, Ulm UniversityInstitute of Protein Biochemistry, Ulm UniversityAbstract Systemic ALys amyloidosis is a debilitating protein misfolding disease that arises from the formation of amyloid fibrils from C-type lysozyme. We here present a 2.8 Å cryo-electron microscopy structure of an amyloid fibril, which was isolated from the abdominal fat tissue of a patient who expressed the D87G variant of human lysozyme. We find that the fibril possesses a stable core that is formed by all 130 residues of the fibril precursor protein. There are four disulfide bonds in each fibril protein that connect the same residues as in the globularly folded protein. As the conformation of lysozyme in the fibril is otherwise fundamentally different from native lysozyme, our data provide a structural rationale for the need of protein unfolding in the development of systemic ALys amyloidosis.https://doi.org/10.1038/s41467-024-54091-7 |
| spellingShingle | Sara Karimi-Farsijani Kartikay Sharma Marijana Ugrina Lukas Kuhn Peter Benedikt Pfeiffer Christian Haupt Sebastian Wiese Ute Hegenbart Stefan O. Schönland Nadine Schwierz Matthias Schmidt Marcus Fändrich Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis Nature Communications |
| title | Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis |
| title_full | Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis |
| title_fullStr | Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis |
| title_full_unstemmed | Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis |
| title_short | Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis |
| title_sort | cryo em structure of a lysozyme derived amyloid fibril from hereditary amyloidosis |
| url | https://doi.org/10.1038/s41467-024-54091-7 |
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