作者
Lei Wei, Ping Jiang, Weixin Xu, Hai Li, Hua Zhang, Liangyu Yan, Mary B Chan-Park, Xue-Wei Liu, Kai Tang, Yuguang Mu, Konstantin Pervushin
发表日期
2011/2/25
期刊
Journal of Biological Chemistry
卷号
286
期号
8
页码范围
6291-6300
出版商
Elsevier
简介
Abnormal aggregation of islet amyloid polypeptide (IAPP) into amyloid fibrils is a hallmark of type 2 diabetes. In this study, we investigated the initial oligomerization and subsequent addition of monomers to growing aggregates of human IAPP at the residue-specific level using NMR, atomic force microscopy, mass spectroscopy, and computational simulations. We found that in solution IAPPs rapidly associate into transient low-order oligomers such as dimers and trimers via interactions between histidine 18 and tyrosine 37. This initial event is proceeded by slow aggregation into higher-order spherical oligomers and elongated fibrils. In these two morphologically distinct types of aggregates IAPPs adopt structures with markedly different residual flexibility. Here we show that the anti-amyloidogenic compound resveratrol inhibits oligomerization and amyloid formation via binding to histidine 18, supporting the finding …
引用总数
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学术搜索中的文章
L Wei, P Jiang, W Xu, H Li, H Zhang, L Yan… - Journal of Biological Chemistry, 2011