Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis
peer-reviewed
Erstveröffentlichung
2019-03-20Authors
Radamaker, Lynn
Lin, Yin-Hsi
Annamalai, Karthikeyan
Huhn, Stefanie
Hegenbart, Ute
Wissenschaftlicher Artikel
Published in
Nature Communications ; 10 (2019). - Art.-Nr. 1103. - eISSN 2041-1723
Link to original publication
https://dx.doi.org/10.1038/s41467-019-09032-0Faculties
Fakultät für NaturwissenschaftenInstitutions
Institut für ProteinbiochemieDocument version
published version (publisher's PDF)Abstract
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 Project THU
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]
Is supplemented by
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
Subject headings
[GND]: Amyloidose[LCSH]: Amyloidosis
[Free subject headings]: Cryoelectron microscopy | Protein aggregation
[DDC subject group]: DDC 570 / Life sciences
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Show full item recordDOI & citation
Please use this identifier to cite or link to this item: 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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