Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts

被引：58

作者：

Chorell, Erik ^{[1
]}

Andersson, Emma ^{[1
]}

Evans, Margery L. ^{[2
]}

Jain, Neha ^{[2
]}

Gotheson, Anna ^{[1
]}

Aden, Jorgen ^{[1
]}

Chapman, Matthew R. ^{[2
]}

Almqvist, Fredrik ^{[1
,3
]}

Wittung-Stafshede, Pernilla ^{[1
]}

机构：

[1] Umea Univ, Dept Chem, Umea, Sweden

[2] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA

[3] Umea Univ, Umea Ctr Microbial Res, Umea, Sweden

来源：

PLOS ONE | 2015年 / 10卷 / 10期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

ESCHERICHIA-COLI; BIOFILM FORMATION; FIELD GRADIENT; IN-VITRO; AGGREGATION; PROTEIN; OLIGOMERS; FIBRILLATION; BIOGENESIS; POLYMERIZATION;

D O I：

10.1371/journal.pone.0140194

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein alpha-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical alpha-synuclein oligomers. We find that CsgE also modulates alpha-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates alpha-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.

引用

页数：11

共 45 条

[1] DnaK/DnaJ/GrpE of Hsp70 system have differing effects on α-synuclein fibrillation involved in Parkinson's disease [J].