Regulation of the assembly and amyloid aggregation of murine amylin by zinc.
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.
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Luiza C S
LC
Erthal
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Adriana F
AF
Marques
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Fábio C L
FC
Almeida
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Gustavo L M
GL
Melo
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Camila M
CM
Carvalho
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Leonardo C
LC
Palmieri
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.
Katia M S
KM
Cabral
Laboratory for Macromolecules (LAMAC-DIMAV), Brazilian National Institute of Metrology, Quality and Technology - INMETRO, Av. N. Sa. das Graças, 50 - Xerém, Duque de Caxias-RJ, 25250-020 Rio de Janeiro, Brazil.
Giselle N
GN
Fontes
School of Pharmacy, Federal University of Rio de Janeiro - UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil; Laboratory for Macromolecules (LAMAC-DIMAV), Brazilian National Institute of Metrology, Quality and Technology - INMETRO, Av. N. Sa. das Graças, 50 - Xerém, Duque de Caxias-RJ, 25250-020 Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil. Electronic address: LML@UFRJ.BR.
Luís Maurício T R
LM
Lima
D000682:Amyloid / Q000096:biosynthesis / Q000187:drug effects; D000818:Animals; D006863:Hydrogen-Ion Concentration; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D066329:Protein Aggregates / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D066329:Protein Aggregates; D015032:Zinc
Amylin; Amyloid; Diabetes; Islet; Islet amyloid polypeptide; Oligomer; Zinc