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Title | Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 875, Year 2021 |
Publish date | Feb 8, 2021 |
Authors | Lynn Radamaker / Julian Baur / Stefanie Huhn / Christian Haupt / Ute Hegenbart / Stefan Schönland / Akanksha Bansal / Matthias Schmidt / Marcus Fändrich / |
PubMed Abstract | Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with ...Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with essentially each patient possessing a unique LC sequence. In this study, we present two ex vivo fibril structures of a λ3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115-residue fibril proteins, mainly from the LC variable domain. The fibril structures imply that a 180° rotation around the disulfide bond and a major unfolding step are necessary for fibrils to form. The two fibril structures show highly similar fibril protein folds, differing in only a 12-residue segment. Remarkably, the two structures do not represent separate fibril morphologies, as they can co-exist at different z-axial positions within the same fibril. Our data imply the presence of structural breaks at the interface of the two structural forms. |
External links | Nat Commun / PubMed:33558536 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.2 - 3.4 Å |
Structure data | EMDB-11030, PDB-6z1i: EMDB-11031, PDB-6z1o: |
Source |
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Keywords | PROTEIN FIBRIL / amyloid fibril / antibody / beta sheet / heart / IMMUNE SYSTEM / amyloid / systemic amyloidosis / light chain |