University of Sussex
Browse

File(s) not publicly available

Structural characterisation of islet amyloid polypeptide fibrils

journal contribution
posted on 2023-06-07, 21:31 authored by O Sumner Makin, Louise SerpellLouise Serpell
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 Å apart. Electron diffraction also revealed the characteristic 4.7 Å 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 Å that has been previously visualised from a single Aß fibre. Together, these data build up a picture of how the IAPP fibril is held together by hydrogen bonded ß-sheet structure and contribute to the understanding of the generic structure of amyloid fibrils.

History

Publication status

  • Published

Journal

Journal of Molecular Biology

ISSN

0022-2836

Issue

5

Volume

335

Page range

1279-1288

Pages

10.0

Department affiliated with

  • Biochemistry Publications

Notes

LS is the corresponding author and wrote the paper. OSM is a student who co-authored and did the analysis. The paper describes the structural analysis of amyloid fibrils formed in Diabetes type 2.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC