Amyloid Fibrillation of Insulin under Water-Limited Conditions
SCIE
SCOPUS
- Title
- Amyloid Fibrillation of Insulin under Water-Limited Conditions
- Authors
- Tae Su Choi; Jong Wha Lee; Kyeong Sik Jin; Kim, HI
- Date Issued
- 2014-10-21
- Publisher
- Cell Press
- Abstract
- Amyloid fibrillation in water-organic mixtures has been widely studied to understand the effect of protein-solvent interactions on the fibrillation process. In this study, we monitored insulin fibrillation in formamide and its methyl derivatives (formamide, N-methyl formamide, N,N-dimethyl formamide) in the presence and absence of water. These model solvent systems mimic the cellular environment by providing denaturing conditions and a hydrophobic environment with limited water content. Thioflavin T (ThT) assay revealed that binary mixtures of water with formamide and its methyl derivatives enhanced fibrillation rates and beta-sheet abundance, whereas organic solvents suppressed insulin fibrillation. We utilized solution small-angle x-ray scattering (SAXS) and differential scanning calorimetry (DSC) to investigate the correlation between protein-solvent interactions and insulin fibrillation. SAXS experiments combined with simulated annealing of the protein indicated that the degree of denaturation of the hydrophobic core region at residues B11-B17 determines the fibrillation rate. In addition, DSC experiments suggested a crucial role of hydrophobic interactions in the fibrillation process. These results imply that an environment with limited water, which imitates a lipid membrane system, accelerates protein denaturation and the formation of intermolecular hydrophobic interactions during amyloid fibrillation.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/9847
- DOI
- 10.1016/J.BPJ.2014.09.008
- ISSN
- 0006-3495
- Article Type
- Article
- Citation
- BIOPHYSICAL JOURNAL, vol. 107, no. 8, page. 1939 - 1949, 2014-10-21
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