The beta-slip: a novel concept in transthyretin amyloidosis.
2000 (English)In: Mol Cell, ISSN 1097-2765, Vol. 6, no 5, 1207-18 p.Article in journal (Refereed) Published
Transthyretin is a tetrameric plasma protein associated with two forms of amyloid disease. The structure of the highly amyloidogenic transthyretin triple mutant TTRG53S/E54D/L55S determined at 2.3 A resolution reveals a novel conformation: the beta-slip. A three-residue shift in beta strand D places Leu-58 at the position normally occupied by Leu-55 now mutated to serine. The beta-slip is best defined in two of the four monomers, where it makes new protein-protein interactions to an area normally involved in complex formation with retinol-binding protein. This interaction creates unique packing arrangements, where two protein helices combine to form a double helix in agreement with fiber diffraction and electron microscopy data. Based on these findings, a novel model for transthyretin amyloid formation is presented.
Place, publisher, year, edition, pages
2000. Vol. 6, no 5, 1207-18 p.
Amino Acid Substitution/genetics, Amyloidosis/genetics/*metabolism, Binding Sites, Crystallography; X-Ray, Epitopes/chemistry/metabolism, Humans, Hydrogen Bonding, Microscopy; Electron, Models; Biological, Models; Molecular, Mutation/genetics, Prealbumin/*chemistry/genetics/*metabolism, Protein Binding, Protein Folding, Protein Interaction Mapping, Protein Structure; Quaternary, Protein Structure; Secondary
IdentifiersURN: urn:nbn:se:umu:diva-13962PubMedID: 11106758OAI: oai:DiVA.org:umu-13962DiVA: diva2:153633