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

janelia7_blocks-janelia7_biblio_header | block

Proceedings of the National Academy of Sciences of the United States of America. 2016 May 16;113(22):6200-5. doi: 10.1073/pnas.1522282113

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

Schmidt A, Annamalai K, Schmidt M, Grigorieff N, Fändrich M

janelia7_blocks-janelia7_biblio_abstract | block

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.

node:body | entity_field

Main Menu (Mobile)- Block

Main Menu - Block

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

Abstract

Janelia Authors