July
[Article]
物理化学学报（WuliHuaxueXuebao）
Acta Phys. -Chim. Sin., 2010, 26(7):2015-2020
2015
www.whxb.pku.edu.cn
小热休克蛋自MiHSP16.5对多肽纤维生长的抑制及对成熟纤维的
解聚作用
曹傲能1,2
汪蔚学2
来鲁华2*
宇文泰然2
邓巍2
C上海大学纳米化学与生物学研究所，上海200444；2北京大学化学与分子工程学院，分子动态与稳态结构国家重点实验室
北京分子科学国家实验室，北京100871)
包括老年痴呆症在内的许多疾病与蛋白质或多肽的淀粉样聚集(纤维化)有关，由于这类疾病的机制尚不
摘要：
清楚，因此还没有有效的预防和治疗手段.研究各种因素如小热休克蛋白对蛋白质或多肽淀粉样聚集的影响对开发防治相关疾病的药物具有重要意义，甲状腺素运载蛋白(TTR)及其突变体很容易形成淀粉样纤维，并与多种疾病相关.MjHSP16.5是一种来源于嗜热古细菌Methanococcus jannaschi的小热休克蛋白，它在酸性条件下具有非常高的分子伴侣活性.本文研究了MjHSP16.5对WTTR肽(在N端添加了色氮酸的TTR105-115片段，序列为WYTIAALLSPYS)纤维化的影响.发现MiHSP16.5能够显著地抑制WTTR肽纤维的生长，且在MiHSP16.5 存在下，WTTR肽形成的纤维比正常条件下形成的要显著细小.尤其是MjHSP16.5还可以使已经成熟的WTTR 肽纤维解离.结果表明，MjHSP16.5抑制多肽纤维的机理可能在于其能够与多肽纤维及纤维种子结合
关键词调：
淀粉样纤维；抑制；解聚；小热休克蛋白；MjHSP16.5
中图分类号：0641
InhibitionofAmvloidFibrillizationandDissociationofMatured
AmyloidFibrilsbyMiHSP16.5
CAO Ao-Neng'2*
WANG Wei-Xue?
YUWEN Tai-Ran?
DENGWej2
LAI Lu-Hua2*
(Institute of Nanochemistry and Nanobiology, Shanghai University,Shanghai200444, P.R.China;
°Beijing National Laboratory of Molecular Sciences, State Key Laboratoryfor Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing100871, P, R. China)
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 its mutants easily form amyloid fibrils and are related to many diseases. Mj HSP16.5, 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 105115 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 WT'TR 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 mechanism was 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
Received: February 1, 2010; Revised: May 10, 2010; Published on Web: May 18, 2010.
*Coresponding author. Email: ancaoshu.edu.cn, Ihlai @pku.edu.cn; Tel: +86-21-66135277, +86-10-62757486.
The project was supported by the National Natural Science Foundation of China (20673003), National Key Basic Research Program of China (973)(2009CB930200), Shanghai Municipal Education Committee, China (09YZ16), and Shanghai Leading Academic Disciplines, China (S30109).
国家自然科学基金(20673003)，国家重点基础研究发展规划项目(973)(2009CB930200)上海市教委(09YZ16)和上海市重点学科(S30109)资助
C Editorial office of Acta Physico-Chimica Sinica