Erlach, Markus Beck and Kalbitzer, Hans Robert and Winter, Roland and Kremer, Werner (2016) Conformational Substates of Amyloidogenic hIAPP Revealed by High Pressure NMR Spectroscopy. CHEMISTRYSELECT, 1 (12). pp. 3239-3243. ISSN 2365-6549,
Full text not available from this repository. (Request a copy)Abstract
The islet amyloid polypeptide (IAPP) is a peptide hormone that is secreted by pancreatic beta cells along with glucagon and insulin. The development of type-2 diabetes mellitus (T2DM) is accompanied by aggregation and amyloid deposits of IAPP. Here we report pressure-induced changes of NMR chemical shifts for the elucidation of conformational substates of IAPP in bulk solution. Comparison with a similar peptide, the Alzheimer peptide Ab, reveals that the area around amino acid residues 3-20 displays large differences in the first and second order pressure coefficients, pinpointing to a different structural ensemble in this sequence element, while the area around amino acid residues 28-37 displays similar transient structural conformations for both peptides. Knowledge of the structural nature of the highly amyloidogenic IAPP and the differences with respect to the conformational ensemble of Ab will help facilitate the rational design of drugs for therapeutic treatment of T2DM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYPEPTIDE FIBRIL FORMATION; ALPHA-HELICAL STATES; CHEMICAL-SHIFTS; PROTEINS; IAPP; MECHANISM; IDENTIFICATION; AGGREGATION; INTERFACES; MEMBRANE; IAPP; diabetes; high pressure NMR; amyloid |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Mar 2019 09:55 |
| Last Modified: | 15 Mar 2019 09:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3499 |
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