Cell Stress and Chaperones

, Volume 15, Issue 4, pp 415–421

Domain a’ of protein disulfide isomerase plays key role in inhibiting α-synuclein fibril formation

Original Paper

DOI: 10.1007/s12192-009-0157-2

Cite this article as:
Cheng, H., Wang, L. & Wang, Cc. Cell Stress and Chaperones (2010) 15: 415. doi:10.1007/s12192-009-0157-2


α-Synuclein (αSyn) 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 αSyn toxicity is poorly understood. In the present study, we found that protein disulfide isomerase (PDI), a stress protein abundant in ER, effectively inhibits αSyn 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 αSyn fibril formation. PDI was further found to be more avid for binding with intermediate species formed during αSyn 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.


Protein disulfide isomeraseα-SynucleinFibrilIsothermal titration calorimetry

Copyright information

© Cell Stress Society International 2009

Authors and Affiliations

  1. 1.National Laboratory of Biomacromolecules, Institute of BiophysicsChinese Academy of SciencesBeijingChina
  2. 2.Graduate School of the Chinese Academy of SciencesBeijingChina