title: The GB1 amyloid fibril: recruitment of the peripheral beta-strands of the domain swapped dimer into the polymeric interface.
abstract: Three-dimensional domain swapping has been evoked as a mechanism for oligomerization of proteins. Here, we show for the immunoglobulin-binding domain B1 of streptococcal protein G (GB1) that fibril formation is observed readily for variants that exist as domain-swapped dimers. No fibril was formed by a revertant that exhibits the stable wild-type GB1 fold or a mutant comprising a highly destabilized, fluctuating ensemble of conformers. Structural features of the GB1 amyloid fibril were characterized by cysteine disulfide cross-linking. Residues in the outer edge beta-strands of the domain-swapped dimer readily form intermolecular disulfide bonds prior to and during fibril formation. On the basis of these data, a structural model for the assembly of domain-swapped dimers into a polymeric structure of the GB1 fibril is proposed.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Louis
authors.forename: In-Ja L
authors.initials: IJ
authors.lastname: Byeon
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baxa
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D001426:Bacterial Proteins; D004220:Disulfides; C034284:IgG Fc-binding protein, Streptococcus; D003545:Cysteine