title: Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril.
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.
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Annamalai
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147 marcus.faendrich@uni-ulm.de niko@grigorieff.org.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Grigorieff
authors.affiliation: Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany; marcus.faendrich@uni-ulm.de niko@grigorieff.org.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D020285:Cryoelectron Microscopy / Q000379:methods*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D007147:Immunoglobulin Light Chains
keywords: Frealix; prion; protein aggregation; protein folding; systemic amyloidosis