Elucidating the Role of C-Terminal Post-Translational Modifications   Using Protein Semisynthesis Strategies: alpha-Synuclein Phosphorylation   at Tyrosine 125

doi:10.1021/ja210866j

CORC > 北京大学 > 生命科学学院

	Elucidating the Role of C-Terminal Post-Translational Modifications Using Protein Semisynthesis Strategies: alpha-Synuclein Phosphorylation at Tyrosine 125
	Hejjaoui, Mirva ; Butterfield, Sara ; Fauvet, Bruno ; Vercruysse, Filip ; Cui, Jia ; Dikiy, Igor ; Prudent, Michel ; Olschewski, Diana ; Zhang, Yan ; Eliezer, David ; Lashuel, Hilal A.
刊名	journal of the american chemical society
	2012
关键词	PARKINSONS-DISEASE SRC-FAMILY INCLUSION FORMATION CELL-DEATH IN-VITRO KINASE LIGATION OLIGOMERIZATION FIBRILLATION MUTATION
DOI	10.1021/ja210866j
英文摘要	Despite increasing evidence that supports the role of different post-translational modifications (PTMs) in modulating alpha-synuclein (alpha-syn) aggregation and toxicity, relatively little is known about the functional consequences of each modification and whether or not these modifications are regulated by each other. This lack of knowledge arises primarily from the current lack of tools and methodologies for the site-specific introduction of PTMs in alpha-syn. More specifically, the kinases that mediate selective and efficient phosphorylation of C-terminal tyrosine residues of alpha-syn remain to be identified. Unlike phospho-serine and phospho-threonine residues, which in some cases can be mimicked by serine/threonine --> glutamate or aspartate substitutions, there are no natural amino acids that can mimic phospho-tyrosine. To address these challenges, we developed a general and efficient semisynthetic strategy that enables the site-specific introduction of single or multiple PTMs and the preparation of homogeneously C-terminal modified forms of alpha-syn in milligram quantities. These advances have allowed us to investigate, for the first time, the effects of selective phosphorylation at Y125 on the structure, aggregation, membrane binding, and subcellular localization of alpha-syn. The development of semisynthetic methods for the site-specific introduction of single or PTMs represents an important advance toward determining the roles of such modifications in alpha-syn structure, aggregation, and functions in heath and disease.; Chemistry, Multidisciplinary; SCI(E); EI; 0; ARTICLE; 11; 5196-5210; 134
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/393552]
专题	生命科学学院
推荐引用方式 GB/T 7714	Hejjaoui, Mirva,Butterfield, Sara,Fauvet, Bruno,et al. Elucidating the Role of C-Terminal Post-Translational Modifications Using Protein Semisynthesis Strategies: alpha-Synuclein Phosphorylation at Tyrosine 125[J]. journal of the american chemical society,2012.
APA	Hejjaoui, Mirva.,Butterfield, Sara.,Fauvet, Bruno.,Vercruysse, Filip.,Cui, Jia.,...&Lashuel, Hilal A..(2012).Elucidating the Role of C-Terminal Post-Translational Modifications Using Protein Semisynthesis Strategies: alpha-Synuclein Phosphorylation at Tyrosine 125.journal of the american chemical society.
MLA	Hejjaoui, Mirva,et al."Elucidating the Role of C-Terminal Post-Translational Modifications Using Protein Semisynthesis Strategies: alpha-Synuclein Phosphorylation at Tyrosine 125".journal of the american chemical society (2012).