5MGQ

Solution structure of oxidized and amidated human IAPP (1-37), the diabetes II peptide.

Summary for 5MGQ

• Entry DOI: 10.2210/pdb5mgq/pdb
• NMR Information: BMRB: 34069
• Descriptor: Islet amyloid polypeptide (1 entity in total)
• Functional Keywords: recombinant human iapp, type ii diabetes, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 3907.31

Authors

Rodriguez Camargo, D.C.,Tripsianes, K.,Reif, B. (deposition date: 2016-11-21, release date: 2017-03-29, Last modification date: 2025-04-09)

Primary citation

Rodriguez Camargo, D.C.,Tripsianes, K.,Buday, K.,Franko, A.,Gobl, C.,Hartlmuller, C.,Sarkar, R.,Aichler, M.,Mettenleiter, G.,Schulz, M.,Boddrich, A.,Erck, C.,Martens, H.,Walch, A.K.,Madl, T.,Wanker, E.E.,Conrad, M.,de Angelis, M.H.,Reif, B.
The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes.
Sci Rep, 7:44041-44041, 2017

PubMed Abstract: Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in β-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an α-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.

PubMed: 28287098
DOI: 10.1038/srep44041

Experimental method

SOLUTION NMR