Regulation of the assembly and amyloid aggregation of murine amylin by zinc

• Published in: Biophysical chemistry Vol. 218; pp. 58 - 70
• Main Authors: Erthal, Luiza C.S., Marques, Adriana F., Almeida, Fábio C.L., Melo, Gustavo L.M., Carvalho, Camila M., Palmieri, Leonardo C., Cabral, Katia M.S., Fontes, Giselle N., Lima, Luís Maurício T.R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2016
• Subjects: Amylin; Amyloid; Amyloid - biosynthesis; Amyloid - drug effects; Animals; Diabetes; Hydrogen-Ion Concentration; Islet; Islet amyloid polypeptide; Islet Amyloid Polypeptide - chemistry; Islet Amyloid Polypeptide - drug effects; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Oligomer; Protein Aggregates - drug effects; Zinc; Zinc - pharmacology; Islet amyloid polypeptide; Amylin; ESI-IMS-MS; IAPP; Amyloid; Diabetes; Islet; Oligomer; Zinc
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2016.09.008

The secretory granule of the pancreatic β-cells is a zinc-rich environment copopulated with the hormones amylin and insulin. The human amylin is shown to interact with zinc ions with major contribution from the single histidine residue, which is absent in amylin from other species such as cat, rhesus and rodents. We report here the interaction of murine amylin with zinc ions in vitro. The self-assembly of murine amylin is tightly regulated by zinc and pH. Ion mobility mass spectrometry revealed zinc interaction with monomers and oligomers. Nuclear magnetic resonance confirms the binding of zinc to murine amylin. The aggregation process of murine amylin into amyloid fibrils is accelerated by zinc. Collectively these data suggest a general role of zinc in the modulation of amylin variants oligomerization and amyloid fibril formation.
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•Zinc interacts with murine amylin as measured by zincon, SPR, fluorescence, IMS, NMR.•Zinc is a heterotrophic modulator of murine amylin assembly and aggregation.•Zinc regulation of amylin does not require the His residue.