6Z1O

AL amyloid fibril from a lambda 3 light chain in conformation A

Summary for 6Z1O

• Entry DOI: 10.2210/pdb6z1o/pdb
• Related: 6IC3
• EMDB information: 11031 4452
• Descriptor: lambda 3 immunoglobulin light chain fragment, residues 2-116 (1 entity in total)
• Functional Keywords: amyloid, antibody, systemic amyloidosis, light chain, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 56587.82

Authors

Radamaker, L.,Fandrich, M. (deposition date: 2020-05-14, release date: 2021-02-24, Last modification date: 2024-10-09)

Primary citation

Radamaker, L.,Baur, J.,Huhn, S.,Haupt, C.,Hegenbart, U.,Schonland, S.,Bansal, A.,Schmidt, M.,Fandrich, M.
Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis.
Nat Commun, 12:875-875, 2021

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 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.

PubMed: 33558536
DOI: 10.1038/s41467-021-21126-2

Experimental method

ELECTRON MICROSCOPY (3.2 Å)