The tachykinin peptide neurokinin B binds copper(I) and silver(I) and undergoes quasi-reversible electrochemistry: towards a new function for the peptide in the brain.

Grosas, Aidan B., Kalimuthu, Palraj, Smith, Alison C., Williams, Peter A., Millar, Thomas J., Bernhardt, Paul V. and Jones, Christopher E. (2014) The tachykinin peptide neurokinin B binds copper(I) and silver(I) and undergoes quasi-reversible electrochemistry: towards a new function for the peptide in the brain.. Neurochemistry International, 70 1: 1-9. doi:10.1016/j.neuint.2014.03.002


Author Grosas, Aidan B.
Kalimuthu, Palraj
Smith, Alison C.
Williams, Peter A.
Millar, Thomas J.
Bernhardt, Paul V.
Jones, Christopher E.
Title The tachykinin peptide neurokinin B binds copper(I) and silver(I) and undergoes quasi-reversible electrochemistry: towards a new function for the peptide in the brain.
Journal name Neurochemistry International   Check publisher's open access policy
ISSN 0197-0186
1872-9754
Publication date 2014-03-17
Sub-type Article (original research)
DOI 10.1016/j.neuint.2014.03.002
Open Access Status
Volume 70
Issue 1
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher Elsevier
Language eng
Subject 2804 Cellular and Molecular Neuroscience
1307 Cell Biology
Abstract The tachykinin neuropeptide family, which includes substance P and neurokinin B, is involved in a wide array of biological functions. Among these is the ability to protect against the neurotoxic processes in Alzheimer's Disease, but the mechanisms driving neuroprotection remain unclear. Dysregulation of metal ions, particularly copper, iron and zinc is a common feature of Alzheimer's Disease, and other amyloidogenic disorders. Copper is known to be released from neurons and recent work has shown that some tachykinins can bind Cu(II) ions, and that neurokinin B can inhibit copper uptake into astrocytes. We have now examined whether neurokinin B is capable of binding Cu(I), which is predicted to be available in the synapse. Using a combination of spectroscopic techniques including cyclic voltammetry and magnetic resonance we show that neurokinin B can bind Cu(I) either directly from added CuCl or by reduction of Cu(II)-bound neurokinin B. The results showed that the Cu(I) binding site differs greatly to that of Cu(II) and involves thioether coordination via Met2 and Met10 and an imidazole nitrogen ligand from His3. The Cu(I) coordination is also different to the site adopted by Ag(I). During changes in oxidation state, copper remains bound to neurokinin B despite large changes to the inner coordination sphere. We predict that neurokinin B may be involved in synaptic copper homeostasis.
Keyword Neurokinin B
Tachykinin
Copper
Peptide
Protein
Metal
Synapse
Copper homeostasis
Neuropeptide
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 28 Mar 2014, 19:37:48 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences