Acta Phys. -Chim. Sin. ›› 2010, Vol. 26 ›› Issue (07): 2015-2020.doi: 10.3866/PKU.WHXB20100708

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Inhibition of Amyloid Fibrillization and Dissociation of Matured Amyloid Fibrils by Mj HSP16.5

CAO Ao-Neng, WANG Wei-Xue, YUWEN Tai-Ran, DENG Wei, LAI Lu-Hua   

  1. Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, P. R. China
    Beijing National Laboratory of Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
  • Received:2010-02-01 Revised:2010-05-10 Published:2010-07-02
  • Contact: CAO Ao-Neng, LAI Lu-Hua E-mail:ancao@shu.edu.cn; lhlai@pku.edu.cn

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Abstract:

The amyloid fibrillization of proteins and peptides is related to many human diseases including Alzheimer's disease. Currently there is no effective therapy for these diseases, because the mechanism of the amyloid fibrillization is still not clear. Understanding how to effectively inhibit amyloid formation will shed light on the prevention and treatment of these diseases. Transtheritin (TTR) and itsmutants easily formamyloid fibrils and are related tomany diseases.MjHSP16.5, a small heat shock protein (SHSP) from Methanococcus jannaschii shows high chaperone-like activity under acidic conditions, and these conditions promote the fibrillization of many peptides. We studied the influence of Mj HSP16.5 on the fibrillization of the peptide WTTR (sequence: WYTIAALLSPYS, i.e., the 105-115 fragment of TTR with a tryptophan added to its N-terminal). Mj HSP16.5 was found to significantly inhibit the growth and maturation of the WTTR fibrils resulting in much thinner fibrils compared to those under normal conditions. More interestingly, Mj SHSP16.5 can dissociate the matured WTTR fibrils. Based on our experimental results, a possible inhibition mechanismwas proposed in which Mj SHP16.5 interacted with WTTR fibrils and/or seeds.

Key words: Amyloid fibril, Inhibition, Dissociation, Small heat shock protein, Mj HSP16.5