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

Publication Type

Journal Article

Year of Publication

2016

Journal

Proc Natl Acad Sci U S A

Volume

113

Pagination

6200–6205

Date Published

05/2016

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.

Keywords

Frealix, prion, Protein aggregation, Protein Folding, systemic amyloidosis

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