+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Characterization of the metal status of natively purified alpha-synuclein from human blood, brain tissue, or recombinant sources using size exclusion ICP-MS reveals no significant binding of Cu, Fe or Zn

Characterization of the metal status of natively purified alpha-synuclein from human blood, brain tissue, or recombinant sources using size exclusion ICP-MS reveals no significant binding of Cu, Fe or Zn

Metallomics 11(1): 128-140

Abnormal protein structure and function have been implicated as the toxic species in many diseases including neurodegenerative diseases, such as Parkinson's. One key pathological hallmark in Parkinson's disease is the formation of Lewy bodies, of which alpha-synuclein is the major component. These Lewy bodies are formed by the aggregation and oligomerization of alpha-synuclein. The oligomeric form of the protein is suspected to be the main contributor to the neurotoxicity seen in the disease. The formation of toxic oligomers has been shown to occur through reactions with lipids, dopamine, hydrogen peroxide as well as metals. The interplay between metals and alpha-synuclein has also been proposed to cause oxidative stress, which promotes the formation of protein aggregates. Most studies investigating the relationship of Cu, Fe and Zn with alpha-synuclein have relied on the use of recombinant protein and there is little evidence that the interaction between metals and alpha-synuclein are physiologically relevant. To address this gap in our knowledge we have characterized the metal content and metal binding capacity of alpha-synuclein purified from human erythrocytes and brain tissue. In addition, we examined the ability of dityrosine cross-linked alpha-synuclein oligomers to bind Cu, Fe and Zn. Using size exclusion chromatography-inductively coupled plasma-mass spectrometry we demonstrated that native human alpha-synuclein, recombinant familial mutants and oligomers do not bind to significant amounts of metal even when they are added to the protein in excess.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 065725241

Download citation: RISBibTeXText

PMID: 30465671

DOI: 10.1039/c8mt00223a

Related references

Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation. Journal of Molecular Biology 378(5): 1104-1115, 2008

Mapping of rat brain using the Synuclein-1 monoclonal antibody reveals somatodendritic expression of alpha-synuclein in populations of neurons homologous to those vulnerable to Lewy body formation in human synucleopathies. Journal of Neuropathology and Experimental Neurology 62(10): 1060-1075, 2003

Raman spectroscopic characterization of secondary structure in natively unfolded proteins: alpha-synuclein. Journal of the American Chemical Society 126(8): 2399-2408, 2004

Interaction of alpha-synuclein with divalent metal ions reveals key differences: a link between structure, binding specificity and fibrillation enhancement. Journal of the American Chemical Society 128(30): 9893-9901, 2006

Characterization of (125I)-SB-258585 binding to human recombinant and native 5-HT6 receptors in rat, pig and human brain tissue. British Journal of Pharmacology 130(7): 1597-1605, 2000

Alpha-synuclein immunoisolation of glial inclusions from multiple system atrophy brain tissue reveals multiprotein components. Journal of Neurochemistry 73(5): 2093-2100, 1999

Characterization of metal binding properties of rhamnogalacturonan II from plant cell walls by size-exclusion HPLC/ICP-MS. Analytical Sciences 20(10): 1389-1393, 2004

Prion-like propagation of human brain-derived alpha-synuclein in transgenic mice expressing human wild-type alpha-synuclein. Acta Neuropathologica Communications 3: 75, 2015

Characterization of Conformational and Dynamic Properties of Natively Unfolded Human and Mouse a-Synuclein Ensembles by NMR: Implication for Aggregation. 2008

Characterization of aggregates of recombinant human factor VIII by size-exclusion chromatography and immunoassay. Biotechnology and Applied Biochemistry 24(1): 55-59, 1996

Refolding of recombinant human interferon alpha-2a from Escherichia coli by urea gradient size exclusion chromatography. Prikladnaia Biokhimiia i Mikrobiologiia 49(1): 17-23, 2013

Immunohistochemical Detection of Alpha-Synuclein in Unfixed Human Brain Tissue. Methods in Molecular Biology 1948: 15-22, 2019

In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain. Journal of Neurochemistry 105(4): 1428-1437, 2008

Characterization of inhibitor-bound alpha-synuclein dimer: role of alpha-synuclein N-terminal region in dimerization and inhibitor binding. Journal of Molecular Biology 395(3): 445-456, 2010

Effects of recombinant human G-CSF, GM-CSF, IL-3, and IL-1 alpha on the growth of purified human peripheral blood progenitors. Blood 76(2): 330-335, 1990