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Ma Dong-Fei, Hou Wen-Qing, Xu Chun-Hua, Zhao Chun-Yu, Ma Jian-Bing, Huang Xing-Yuan, Jia Qi, Ma Lu, Liu Cong, Li Ming, Lu Ying
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  • α-synuclein (α-syn) is a key protein involved in Parkinson’s disease. There have been many researches about α-syn in recent years. It was suggested that the aggregation of α-syn may induce the lipid membranes to disrupted, which is related to the pathology of neurodegenerative diseases. Thus the studying of the dynamics of α-syn on membranes, especially in the presence of high-concentration protein, is important for understanding its function and its role in the pathology. In this study, we use LipoFRET, a single molecule method based on the principle of energy transfer between the donor labeled on the biomolecule and the quenchers encapsulated in the liposome. The quenchers encapsulated in liposomes attenuate the fluorescence attached to membrane proteins near the membrane, or penetrating in the membranes. If interesting site of membrane protein can be labeled, the LipoFRET could probe positional changes of a single membrane protein in the direction normal to the membrane. In the research of α-syn by LipoFRET, some interesting results can be obtained with different concentrations of protein. On the one hand, with the increase of concentration of α-syn in solution, the centre domain of α-syn can leave the surface of the lipid bilayer and enter into the aqueous solution. However, this domain of α-syn is located around the membrane surface at low concentration. On the other hand, the N-terminus of α-syn with three main positions at low concentration of protein, maintains three but different positions in the membrane at high concentration, where each position is closer to or above the outer surface of liposome. The above phenomena suggeste that the interaction between α-syn and membranes might be weakened with the increase of concentration of protein. At the same time, with single molecule fluorescence imaging, we also observe the promoted dissociation rates for individual fluorophore labeled α-syn from liposomes with high concentration of unlabeled proteins in solution. The result is consistent with the result of our single-molecule experiment with LipoFRET. Along with the results from LipoFRET, it could be indicated that there is a competition process where each α-syn could be occupied by the other one at high protein concentration, which leads to the dissociation. The concentration-dependent dissociation may be the property that regulates the aggregation of α-syn in vivo, which is one of the important factors that influence the pathology of the neurodegenerative diseases.
        Corresponding author:Lu Ying,yinglu@iphy.ac.cn
      • Funds:Project supported by the National Science Foundation of China (Grant Nos. 11674382, 11834018, 91753104, 11574381), the CAS Key Research Program of Frontier Sciences (Grant No. QYZDJ-SSW-SYS014), and the Youth Innovation Promotion Association of CAS, China (No. 2017015)
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    • 名称 氨基酸序列(1—140)
      Human
      α-synuclein
      MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVL
      YVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAV
      AQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDM
      PVDPDNEAYEMPSEEGYQDYEPEA
      DownLoad: CSV
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    Metrics
    • Abstract views:8669
    • PDF Downloads:81
    • Cited By:0
    Publishing process
    • Received Date:21 October 2019
    • Accepted Date:10 November 2019
    • Published Online:05 February 2020

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