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Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril

TitleCryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril
Publication TypeJournal Article
Year of Publication2016
AuthorsSchmidt, A, Annamalai K, Schmidt M, Grigorieff N, Marcus Fändrich M
Refereed DesignationRefereed
JournalProc Natl Acad Sci U S A
Volume113
Pagination6200–6205
Date Published05/2016
KeywordsFrealix, prion, Protein aggregation, Protein Folding, systemic amyloidosis
Abstract

Amyloid fibrils are proteinaceous aggregates associated with diseases in humans and animals. The fibrils are defined by intermolecular interactions between the fibril-forming polypeptide chains, but it has so far remained difficult to reveal the assembly of the peptide subunits in a full-scale fibril. Using electron cryomicroscopy (cryo-EM), we present a reconstruction of a fibril formed from the pathogenic core of an amyloidogenic immunoglobulin (Ig) light chain. The fibril density shows a lattice-like assembly of face-to-face packed peptide dimers that corresponds to the structure of steric zippers in peptide crystals. Interpretation of the density map with a molecular model enabled us to identify the intermolecular interactions between the peptides and rationalize the hierarchical structure of the fibril based on simple chemical principles.

DOI10.1073/pnas.1522282113
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