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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
Author(s) -
Yoon Soyoung,
Kim Soohyun,
Im Hana,
Lee Kyunghee
Publication year - 2017
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.11282
Subject(s) - fusion protein , amyloid (mycology) , chemistry , fibril , islet , ligand (biochemistry) , fusion , microbiology and biotechnology , biophysics , mutant , amyloid disease , maltose binding protein , amyloid fibril , biochemistry , recombinant dna , biology , receptor , amyloid β , medicine , inorganic chemistry , linguistics , philosophy , disease , pathology , endocrinology , insulin , gene
Human islet amyloid polypeptide (hIAPP) is converted to toxic aggregates in type‐2 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. FKBPIF‐L23‐hIAPP and F36VIF‐L23‐hIAPP accelerated amyloid fibril formation. Assays of cis / trans ‐peptidyl‐prolyl isomerase activity as well as chaperone activity of FKBPIF‐L23‐hIAPP 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 FKBPIF‐L23‐hIAPP fusion protein. Deletion mutant analysis of the insertion‐in‐flap (IF) domain revealed that the C‐terminal half is essential for acceleration of amyloid fibril formation. Based on these observations, we suggested a potential anti‐T2D therapeutic strategy by means of a small ligand and fragments of the IF domain inserted in a fusion protein.