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TitleCryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 875, Year 2021
Publish dateFeb 8, 2021
AuthorsLynn Radamaker / Julian Baur / Stefanie Huhn / Christian Haupt / Ute Hegenbart / Stefan Schönland / Akanksha Bansal / Matthias Schmidt / Marcus Fändrich /
PubMed AbstractSystemic 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 linksNat Commun / PubMed:33558536 / PubMed Central
MethodsEM (helical sym.)
Resolution3.2 - 3.4 Å
Structure data

EMDB-11030, PDB-6z1i:
AL amyloid fibril from a lambda 3 light chain in conformation B
Method: EM (helical sym.) / Resolution: 3.4 Å

EMDB-11031, PDB-6z1o:
AL amyloid fibril from a lambda 3 light chain in conformation A
Method: EM (helical sym.) / Resolution: 3.2 Å

Source
  • homo sapiens (human)
  • Human (human)
KeywordsPROTEIN FIBRIL / amyloid fibril / antibody / beta sheet / heart / IMMUNE SYSTEM / amyloid / systemic amyloidosis / light chain

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