Zinc–Ligand Interactions Modulate Assembly and Stability of the Insulin Hexamer – A Review

@article{Dunn2005ZincLigandIM,
  title={Zinc–Ligand Interactions Modulate Assembly and Stability of the Insulin Hexamer – A Review},
  author={Michael F. Dunn},
  journal={Biometals},
  year={2005},
  volume={18},
  pages={295-303}
}
  • M. Dunn
  • Published 1 August 2005
  • Biology, Chemistry
  • Biometals
Zinc and calcium ions play important roles in the biosynthesis and storage of insulin. Insulin biosynthesis occurs within the β-cells of the pancreas via preproinsulin and proinsulin precursors. In the golgi apparatus, proinsulin is sequestered within Zn2+- and Ca2+-rich storage/secretory vesicles and assembled into a Zn2+ and Ca2+ containing hexameric species, (Zn2+)2(Ca2+)(Proin)6. In the vesicle, (Zn2+)2(Ca2+)(Proin)6 is converted to the insulin hexamer, (Zn2+)2(Ca2+)(In)6, by excision of… 

Thermodynamic contributions to the stability of the insulin hexamer.

The insulin hexamer is resistant to degradation and fibrillation, which makes it an important quaternary structure for its in vivo storage in Zn(2+)- and Ca(2+)-rich vesicles in the pancreas and for

Zinc and insulin in pancreatic beta-cells

The Zn 2+ homeostasis in β-cells is discussed with emphasis on the potential signaling role of Zn2+ to islet biology, and the relationship between co-stored Zn3+ and insulin undoubtedly is critical to normal β-cell function.

Affinity of zinc and copper ions for insulin monomers.

Insulin cannot form complexes with zinc ions in circulation due to the low concentration of free Zn(2+) in this environment, and it is demonstrated that insulin cannot form complex with Cu(2+)-insulin complex.

Thermodynamics of formation of the insulin hexamer: metal-stabilized proton-coupled assembly of quaternary structure.

Analyzing the thermodynamics of formation of the insulin hexamer reveals that two to three H(+) bind to the hexamer upon its formation at pH 7.4, which is both enthalpically and entropically favored.

Identification of the Zn2+ Binding Site and Mode of Operation of a Mammalian Zn2+ Transporter*

Fluorescence-based functional analysis and structural modeling are combined to identify the zinc binding site of ZnT proteins essential for zinc transport and indicate, for the first time, that Zn2+ transport mediated by a mammalian ZNT is catalyzed by H+/Zn 2+ exchange.

Insights into the Dynamics of the Human Zinc Transporter ZnT8 by MD Simulations

The dimer interface that keeps the two TM channels in contact became looser in both variants upon zinc binding to the transport site, suggesting that this may be an important step toward the switch from the inward- to the outward-facing state of the protein.

Investigation of non-covalent complexations of Ca(II) and Mg(II) ions with insulin by using electrospray ionization mass spectrometry.

The binding equilibrium constants of Ca(II- and Mg(II)-insulin non-covalent complexes have been determined successfully by ESI-MS.

Zinc-Induced Conformational Transitions in Human Islet Amyloid Polypeptide and Their Role in the Inhibition of Amyloidosis.

It appears that zinc preferentially stabilizes the β-hairpin conformation of hIAPP and the population of zinc-bound hI APP in solution determines what effect this has on amyloid aggregation, whereas physiological zinc concentrations have an inhibitory effect.
...

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The Glu(B13) carboxylates of the insulin hexamer form a cage for Cd2+ and Ca2+ ions.

Insulin solutions to which both Cd2+ and Co2+ have been added in a ratio of 6:2:1 followed by oxidation to the exchange-inert Co3+ state yield stable hybrid species containing both Co3- and Cd1+ with a composition of (In)6(Co3+)2Cd2+.

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