Bulletin of the Korean Chemical Society | |
Regulation of Amyloid Fibril Formation from Human Islet Amyloid Polypeptide by a Ligand Binding to the Fusion of FK506‐binding Protein and the Insertion‐in‐Flap Domain | |
Kyunghee Lee1  Soohyun Kim1  Soyoung Yoon2  Hana Im2  | |
[1] 747 Korea;Department of Chemistry Sejong University Seoul 143‐Department of Molecular Biology Sejong University Seoul 143‐ | |
关键词: Human islet amyloid polypeptide; FK506‐; binding protein with insertion‐; in‐; flap; FK506; Thioflavin T fluorescence; Transmission electron microscopy; | |
DOI : 10.1002/bkcs.11282 | |
学科分类:化学(综合) | |
来源: Korean Chemical Society | |
【 摘 要 】
Human islet amyloid polypeptide (hIAPP) is converted to toxic aggregates in typeâ2 diabetes (T2D). With the aim of developing a candidate agent regulating hIAPP amyloid fibril formation, we constructed a series of recombinant fusion proteins using a bacterial expression system. FKBPIFâL23âhIAPP and F36VIFâL23âhIAPP accelerated amyloid fibril formation. Assays of cis/transâpeptidylâprolyl isomerase activity as well as chaperone activity of FKBPIFâL23âhIAPP fusion proteins suggested that amyloid fibrils were produced because the chaperone activity of FKBPIF in the form of fusion protein was diminished. Moreover, addition of FK506, a binding ligand, slowed down the process of amyloid fibril formation in FKBPIFâL23âhIAPP fusion protein. Deletion mutant analysis of the insertionâinâflap (IF) domain revealed that the Câterminal half is essential for acceleration of amyloid fibril formation. Based on these observations, we suggested a potential antiâT2D therapeutic strategy by means of a small ligand and fragments of the IF domain inserted in a fusion protein.
【 授权许可】
Unknown
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