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Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation
Cheng, Han1,2; Wang, Lei1; Wang, Chih-chen1
刊名Cell stress & chaperones
2010-07-01
卷号15期号:4页码:415-421
关键词Protein disulfide isomerase Alpha-synuclein Fibril Isothermal titration calorimetry
ISSN号1355-8145
DOI10.1007/s12192-009-0157-2
通讯作者Wang, chih-chen(chihwang@sun5.ibp.ac.cn)
英文摘要Alpha-synuclein (alpha syn) is the main component of lewy bodies formed in midbrain dopaminergic neurons which is a pathological characteristic of parkinson's disease. it has been recently showed to induce endoplasmic reticulum (er) stress and impair er functions. however, the mechanism of how er responds to alpha syn toxicity is poorly understood. in the present study, we found that protein disulfide isomerase (pdi), a stress protein abundant in er, effectively inhibits alpha syn fibril formation in vitro. in pdi molecule with a structure of abb'xa'c, domain a' was found to be essential and sufficient for pdi to inhibit alpha syn fibril formation. pdi was further found to be more avid for binding with intermediate species formed during alpha syn fibril formation, and the binding was more intensive in the later lag phase. our results provide new insight into the role of pdi in protecting er from the deleterious effects of misfolded protein accumulation in many neurodegenerative diseases.
WOS关键词ENDOPLASMIC-RETICULUM STRESS ; PARKINSONS-DISEASE ; MOLECULAR CHAPERONES ; BINDING SITE ; IN-VITRO ; MUTATION ; FAMILY ; GENE ; IDENTIFICATION ; PATHOGENESIS
WOS研究方向Cell Biology
WOS类目Cell Biology
语种英语
出版者SPRINGER
WOS记录号WOS:000278681300008
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2413055
专题中国科学院大学
通讯作者Wang, Chih-chen
作者单位1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Cheng, Han,Wang, Lei,Wang, Chih-chen. Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation[J]. Cell stress & chaperones,2010,15(4):415-421.
APA Cheng, Han,Wang, Lei,&Wang, Chih-chen.(2010).Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation.Cell stress & chaperones,15(4),415-421.
MLA Cheng, Han,et al."Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation".Cell stress & chaperones 15.4(2010):415-421.
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