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EnglishIslet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+ but also to bring into light a coordination shell further stabilized by non-covalent interactions.
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| Titolo: | Zinc interactions with a soluble mutated rat amylin to mimic whole human amylin. An experimental and simulation approach to understand stoichiometry, speciation and coordination of the metal complexes |
| Autori: | |
| Data di pubblicazione: | 2020 |
| Rivista: | |
| Abstract: | Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+ but also to bring into light a coordination shell further stabilized by non-covalent interactions. |
| Handle: | http://hdl.handle.net/11388/234470 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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