Formation of low-dimensional crystalline nucleus region during insulin amyloidogenesis process

Journal Article · Fri Mar 09 04:00:00 EST 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.01.153· OSTI ID:22207741

Amdursky, Nadav; Gazit, Ehud ^[1]; Rosenman, Gil ^[2]

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1. Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel)
2. School of Electrical Engineering, Iby and Aladar Fleischman, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel)

Highlights: Black-Right-Pointing-Pointer We observe lag-phase crystallization process in insulin. Black-Right-Pointing-Pointer The crystallization is a result of the formation of higher order oligomers. Black-Right-Pointing-Pointer The crystallization also changes the secondary structure of the protein. Black-Right-Pointing-Pointer The spectroscopic signature can be used for amyloid inhibitors assay. -- Abstract: Insulin, as other amyloid proteins, can form amyloid fibrils at certain conditions. The self-assembled aggregation process of insulin can result in a variety of conformations, starting from small oligomers, going through various types of protofibrils, and finishing with bundles of fibrils. One of the most common consensuses among the various self-assembly processes that are suggested in the literature is the formation of an early stage nucleus conformation. Here we present an additional insight for the self-assembly process of insulin. We show that at the early lag phase of the process (prior to fibril formation) the insulin monomers self-assemble into ordered nanostructures. The most notable feature of this early self-assembly process is the formation of nanocrystalline nucleus regions with a strongly bound electron-hole confinement, which also change the secondary structure of the protein. Each step in the self-assembly process is characterized by an optical spectroscopic signature, and possesses a narrow size distribution. By following the spectroscopic signature we can measure the potency of amyloid fibrils inhibitors already at the lag phase. We further demonstrate it by the use of epigallocatechin gallate, a known inhibitor for insulin fibrils. The findings can result in a spectroscopic-based application for the analysis of amyloid fibrils inhibitors.

• OSTI ID: 22207741
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 419; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGGLOMERATION
CRYSTALLIZATION
CRYSTALS
INSULIN
MONOMERS
NANOSTRUCTURES
SPECTROSCOPY