Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis
peer-reviewed
Erstveröffentlichung
2019-03-20Autoren
Radamaker, Lynn
Lin, Yin-Hsi
Annamalai, Karthikeyan
Huhn, Stefanie
Hegenbart, Ute
Wissenschaftlicher Artikel
Erschienen in
Nature Communications ; 10 (2019). - Art.-Nr. 1103. - eISSN 2041-1723
Link zur Originalveröffentlichung
https://dx.doi.org/10.1038/s41467-019-09032-0Fakultäten
Fakultät für NaturwissenschaftenInstitutionen
Institut für ProteinbiochemieDokumentversion
Veröffentlichte Version (Verlags-PDF)Zusammenfassung
Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of mortality. Here we report the structure of a λ1 AL amyloid fibril from an explanted human heart at a resolution of 3.3 Å which we determined using cryo-electron microscopy. The fibril core consists of a 91-residue segment presenting an all-beta fold with ten mutagenic changes compared to the germ line. The conformation differs substantially from natively folded light chains: a rotational switch around the intramolecular disulphide bond being the crucial structural rearrangement underlying fibril formation. Our structure provides insight into the mechanism of protein misfolding and the role of patient-specific mutations in pathogenicity.
DFG-Projekt uulm
SFB 1279 Teilprojekt A03 / Mechanismus und Struktur von Peptidfibrillen, die Virusinfektionen beeinflussen / DFG / 316249678
Strukturelle Analyse von SAA-Amyloidfibrillen mittels kryo-EM und NMR / DFG / 313913757 [SCHM 3276/1]
Strukturelle Analyse von SAA-Amyloidfibrillen mittels kryo-EM und NMR / DFG / 313913757 [SCHM 3276/1]
Wird ergänzt durch
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-019-09032-0/MediaObjects/41467_2019_9032_MOESM1_ESM.pdfhttps://static-content.springer.com/esm/art%3A10.1038%2Fs41467-019-09032-0/MediaObjects/41467_2019_9032_MOESM2_ESM.pdf
Schlagwörter
[GND]: Amyloidose[LCSH]: Amyloidosis
[Freie Schlagwörter]: Cryoelectron microscopy | Protein aggregation
[DDC Sachgruppe]: DDC 570 / Life sciences
Metadata
Zur LanganzeigeDOI & Zitiervorlage
Nutzen Sie bitte diesen Identifier für Zitate & Links: http://dx.doi.org/10.18725/OPARU-48914
Radamaker, Lynn et al. (2023): Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-48914
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