Molecular understanding of copper and iron interaction with alpha-synuclein by fluorescence analysis.
Alpha-synuclein aggregation is a hallmark pathological feature in Parkinson's disease (PD). The conversion of alpha-synuclein from a soluble monomer to an insoluble fibril may underlie the neurodegeneration associated with PD. Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. In the present investigation, we analyzed the binding efficiency of Cu and Fe to alpha-synuclein by fluorescence studies. It is interesting to note that Cu and Fe showed differential binding pattern toward alpha-synuclein (wild type and A30P, A53T, and E46K mutant forms) as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. The experimental data might prove useful in understanding the hierarchy of metals binding to alpha-synuclein and its role in neurodegeneration.
Bharathi
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.
Rao
K S J
KS
D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D052160:Benzothiazoles; D001665:Binding Sites / Q000502:physiology; D003300:Copper / Q000737:chemistry* / Q000378:metabolism*; D005453:Fluorescence; D005456:Fluorescent Dyes; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013844:Thiazoles / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
D000817:Anilino Naphthalenesulfonates; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T; D014443:Tyrosine; C027132:1-anilino-8-naphthalenesulfonate; D003300:Copper; D007501:Iron