Binding of alpha-synuclein with Fe(III) and with Fe(II) and biological implications of the resultant complexes

作者：Peng, Yong; Wang, Chengshan; Xu, Howard H.; Liu, You-Nian^*; Zhou, Feimeng

来源：Journal of Inorganic Biochemistry, 2010, 104(4): 365-370.

DOI：10.1016/j.jinorgbio.2009.11.005

• alpha-Synuclein
• Iron
• Binding affinity
• Oxidative stress
• Parkinson's disease

Parkinson's disease (PD) is hallmarked by the abnormal intracellular inclusions (Lewy bodies or LBs) in dopaminergic cells. Amyloidogenic protein alpha-synuclein (alpha-syn) and iron (including both Fe(Ill) and Fe(II)) are both found to be present in LBs. The interaction between iron and alpha-syn might have important biological relevance to PD etiology. Previously, a moderate binding affinity between alpha-syn and Fe(II) (5.8 x 10(3) M-1) has been measured, but studies on the binding between alpha-syn and Fe(III) have not been reported. In this work, electrospray mass spectrometry (ES-MS), cyclic voltammetry (CV), and fluorescence spectroscopy were used to study the binding between alpha-syn and Fe(II) and the redox property of the resultant alpha-syn-Fe(II) complex. The complex is of a 1: 1 stoichiometry and can be readily oxidized electrochemically and chemically (by O-2) to the putative alpha-syn-Fe(III) complex, with H2O2 as a co-product. The reduction potential was estimated to be 0.025 V vs. Ag/AgCl, which represents a shift by -0.550 V vs. the standard reduction potential of the free Fe(III)/Fe(II) couple. Such a shift allows a binding constant between alpha-syn and Fe(III), 1.2 x 10(13) M-1, to be deduced. Despite the relatively high binding affinity, alpha-syn-Fe(III) generated from the oxidation of alpha-syn-Fe(II) still dissociates due to the stronger tendency of Fe(III) to hydrolyze to Fe(OH)(3) and/or ferrihydrite gel. The roles of alpha-syn and its interaction with Fe(III) and/or Fe(II) are discussed in the context of oxidative stress, metal-catalyzed alpha-syn aggregation, and iron transfer processes.

• 出版日期2010-4
• 单位中南大学