小肽促进α-突触核蛋白正常折叠的研究

Promotion of correct folding of α-synuclein by small peptides

目的：在大肠杆菌中研究小肽促进α-突触核蛋白（α—synuclein，α—Syn）（A53T，S129A）的正常折叠。方法：利用分子生物学和生物信息学技术，以α-Syn的疏水区域为基础，设计了4种小肽（Pn：P1-P4）；构建融合蛋白α-Syn—GFP，使α-Syn基因位于GFP上游，各种小肽以双顺反子方式与α-Syn—GFP共同表达；以文献报道的有效促进α-Syn正常折叠的小肽Pc（MGGAVVTGR）为对照，利用融合蛋白折叠在细菌中可视化技术研究小肽Pn影响α-Syn（A53T，S129A）的正常折叠的效果。结果：4种小肽均能更好地促进α-Syn（S129A）的正常折叠；和对照Pc相比，小肽P2（MRGGAVVTGR）使α-Syn（A53T）正常折叠提高了10％，小肽P4（MRVGGAVVR）使α-Syn（S129A）正常折叠提高了83％。结论：在大肠杆菌中，小肽可以不同程度的促进α-Syn（A53T，S129A）的正常折叠。

Objective：To study the promotion of correct folding of α-synuclein （α-Syn） （ A53T, S129A） in Escherichia coli by small peptide. Methods： The target gene was fused at upstream of GFP to give rise to α-Syn-GFP. Four small peptides （ Pn ： P1 - P4） which came from the hydrophobic region of α-Syn were co-expressed with α-Syn-GFP by a hicistronic format. Using the small peptide Pc （MGGAVVTGR） as a control,the ability of the four small peptides to increase the correct folding of α-Syn （A53T, S129A） in E. coli was studied by visualization technology of fusion protein interaction in bacteria. Results： The four small peptides could increase the correct folding of α-Syn （A53T, S129A ）. Small peptide P2 could increase the correct folding of α-Syn（A53T） by 10%, and P4 could increase the correct folding of α-Syn （S129A）by 83% compared with Pc. Conclusion： The design of the experiment is feasible. Small peptides can increase the correct folding of α-Syn （A53T, S129 A） in E. coll.