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Publication Abstract from PubMed

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 lambda3 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 degrees 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.

Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis.,Radamaker L, Baur J, Huhn S, Haupt C, Hegenbart U, Schonland S, Bansal A, Schmidt M, Fandrich M Nat Commun. 2021 Feb 8;12(1):875. doi: 10.1038/s41467-021-21126-2. PMID:33558536^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.