A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein

	A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein
	Du, HN; Tang, L; Luo, XY; Li, HT; Hu, J; Zhou, JW; Hu, HY
刊名	BIOCHEMISTRY
	2003
卷号	42 期号:29 页码:8870-8878
通讯作者	Hu, HY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, Shanghai 200031, Peoples R China.,
英文摘要	Amyloid-like aggregation or fibrillization of alpha-synuclein (alpha-Syn) and the filamentous deposits in Lewy bodies are believed to be closely associated with several fatal neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Here, we report the importance of a nine-residue peptide Motif, (66)VGGAVVTGV(74), in the fibrillization and cytotoxicity of human alpha-Syn. Mutagenesis combined with thioflavin T fluorescence detection, atomic force microscopic imaging, and cytotoxicity assays reveal that deletion of this sequence completely eliminates alpha-Syn fibrillization and cell toxicity. However, deletion of the (71)VTGV(74) sequence decreases the fibrillization rate while the cytotoxicity remains unchanged. Incorporation of charged residues within this region slows aggregation and even impedes filament formation. In addition, substitution of Gly68 with Ala or C-terminal truncations of alpha-Syn accelerate the fibrillization processes. Circular dichroism studies suggest that beta-sheet formation is often concomitant with filament formation. Thus, this segment, namely, the GAV motif, is responsible for aggregation or fibrillization of alpha-Syn and perhaps other amyloidogenic proteins. The oligomers formed during fibrillogenesis might be associated with the cytotoxicities of various alpha-Syn species. This finding may provide further insight into the understanding of the molecular mechanism underlying the fibrillogenesis implicated in neurodegeneration as well as aid in drug design and development of transgenic models.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ABNORMAL PROTEIN AGGREGATION ; A-BETA COMPONENT ; PARKINSONS-DISEASE ; ALZHEIMERS-DISEASE ; PRION PROTEIN ; SPIDER SILK ; IN-VITRO ; SHEET ; TOXICITY ; FIBRILS
收录类别	SCI
语种	英语
WOS记录号	WOS:000184390600025
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2389]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Du, HN,Tang, L,Luo, XY,et al. A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein[J]. BIOCHEMISTRY,2003,42(29):8870-8878.
APA	Du, HN.,Tang, L.,Luo, XY.,Li, HT.,Hu, J.,...&Hu, HY.(2003).A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein.BIOCHEMISTRY,42(29),8870-8878.
MLA	Du, HN,et al."A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein".BIOCHEMISTRY 42.29(2003):8870-8878.