Structural characterisation of islet amyloid polypeptide fibrils.
Islet amyloid is found in many patients suffering from type 2 diabetes. Amyloid fibrils found deposited in the pancreatic islets are composed of a 37-residue peptide, known as islet amyloid polypeptide (IAPP) (also known as amylin) and are similar to those found in other amyloid diseases. Synthetic IAPP peptide readily forms amyloid fibrils in vitro and this has allowed fibril formation kinetics and the overall morphology of IAPP amyloid to be studied. Here, we use X-ray fibre diffraction, electron microscopy and cryo-electron microscopy to examine the molecular structure of IAPP amyloid fibrils. X-ray diffraction from aligned synthetic amyloid fibrils gave a highly oriented diffraction pattern with layer-lines spaced 4.7 A apart. Electron diffraction also revealed the characteristic 4.7 A meridional signal and the position of the reflection could be compared directly to the image of the diffracting unit. Cryo-electron microscopy revealed the strong signal at 4.7 A that has been previously visualised from a single Abeta fibre. Together, these data build up a picture of how the IAPP fibril is held together by hydrogen bonded beta-sheet structure and contribute to the understanding of the generic structure of amyloid fibrils.
Sumner Makin
O
O
University of Cambridge, Structural Medicine Unit, Cambridge Institute for Medical Research and Department of Haematology, Hills Rd, Cambridge CB2 2XY, UK.
Serpell
Louise C
LC
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000897:Anti-Ulcer Agents / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D006801:Humans; D006860:Hydrogen Bonding; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000737:chemistry / Q000648:ultrastructure; D008854:Microscopy, Electron; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
D000682:Amyloid; D000897:Anti-Ulcer Agents; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments