Findings from University of Saskatchewan Update Understanding of Catecholamines [Cu(II) and dopamine bind to alpha-synuclein and cause large conformational changes]
By a News Reporter-Staff News Editor at Life Science Weekly -- Data detailed on Catecholamines have been presented. According to news reporting from Saskatoon, Canada, by NewsRx journalists, research stated, "Alpha-Synuclein (AS) is an intrinsically disordered protein that can misfold and aggregate to form Lewy bodies in dopaminergic neurons, a classic hallmark of Parkinson's disease. The binding of Cu(II) and dopamine to AS was evaluated by nanopore analysis with alpha-hemolysin."
The news correspondents obtained a quote from the research from the University of Saskatchewan, "In the absence of Cu(II), wild-type AS (1 mu M) readily translocated through the pore with a blockade current of - 85 pA, but mostly bumping events were observed in the presence of 25 mu M Cu(II). A binding site in the N-terminus was confirmed, because Cu(II) had no effect on the event profile of a peptide consisting of the C-terminal 96-140 residues. In the presence of dopamine (25 mu M), the translocation events at - 85 pA shifted to - 80 pA, which also represents translocation events, because the event time decreases with increasing voltage. Events at - 80 pA were also observed for the mutant A30P AS in the presence of dopamine. Event profiles for an N-terminal 1-60-residue peptide and a C-terminal 96-140-residue peptide were both altered in the presence of 25 mu M dopamine. In contrast, dopamine had little effect on the CD spectrum of AS, and a single binding site with a K-a of 3.5 x 10(3) M-1 was estimated by isothermal titration calorimetry. Thus, dopamine can interact with both the N-terminus and the C-terminus. Two-dimensional NMR spectroscopy of AS in the presence of dopamine showed that there were significant changes in the spectra in all regions of the protein. According to these findings, a model is presented in which dopamine induces folding between the N-terminus and C-terminus of AS."
According to the news reporters, the research concluded: "Partially folding conformations such as this may represent important intermediates in the misfolding of AS that leads to fibrillization."
For more information on this research see: Cu(II) and dopamine bind to alpha-synuclein and cause large conformational changes. FEBS Journal, 2014;281(12):2738-2753. FEBS Journal can be contacted at: Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - www.wiley.com/; FEBS Journal - onlinelibrary.wiley.com/journal/10.1111/(ISSN)1742-4658)
Our news journalists report that additional information may be obtained by contacting O. Tavassoly, University of Saskatchewan, Dept. of Biochem, Saskatoon, SK S7N 0W0, Canada. Additional authors for this research include S. Nokhrin, O.Y. Dmitriev and J.S. Lee (see also Catecholamines).
Keywords for this news article include: Canada, Dopamine, Saskatoon, Saskatchewan, Catecholamines, Biogenic Amines, alpha-Synuclein, Organic Chemicals, Nerve Tissue Proteins, North and Central America
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