Amyloid fibrillation of insulin under water-limited conditions

Tae Su Choi, Jong Wha Lee, Kyeong Sik Jin, Hugh I. Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 β-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.

Original languageEnglish
Pages (from-to)1939-1949
Number of pages11
JournalBiophysical Journal
Volume107
Issue number8
DOIs
Publication statusPublished - 2014 Oct 21
Externally publishedYes

Fingerprint

Amyloid
Insulin
Water
Differential Scanning Calorimetry
Hydrophobic and Hydrophilic Interactions
X-Rays
Protein Denaturation
Dimethylformamide
Proteins
Membrane Lipids
formamide

ASJC Scopus subject areas

  • Biophysics

Cite this

Amyloid fibrillation of insulin under water-limited conditions. / Choi, Tae Su; Lee, Jong Wha; Jin, Kyeong Sik; Kim, Hugh I.

In: Biophysical Journal, Vol. 107, No. 8, 21.10.2014, p. 1939-1949.

Research output: Contribution to journalArticle

Choi, Tae Su ; Lee, Jong Wha ; Jin, Kyeong Sik ; Kim, Hugh I. / Amyloid fibrillation of insulin under water-limited conditions. In: Biophysical Journal. 2014 ; Vol. 107, No. 8. pp. 1939-1949.
@article{334102f0d1ec49729ceeda6313a16537,
title = "Amyloid fibrillation of insulin under water-limited conditions",
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 β-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.",
author = "Choi, {Tae Su} and Lee, {Jong Wha} and Jin, {Kyeong Sik} and Kim, {Hugh I.}",
year = "2014",
month = "10",
day = "21",
doi = "10.1016/j.bpj.2014.09.008",
language = "English",
volume = "107",
pages = "1939--1949",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "8",

}

TY - JOUR

T1 - Amyloid fibrillation of insulin under water-limited conditions

AU - Choi, Tae Su

AU - Lee, Jong Wha

AU - Jin, Kyeong Sik

AU - Kim, Hugh I.

PY - 2014/10/21

Y1 - 2014/10/21

N2 - 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 β-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.

AB - 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 β-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.

UR - http://www.scopus.com/inward/record.url?scp=84908225375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908225375&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2014.09.008

DO - 10.1016/j.bpj.2014.09.008

M3 - Article

C2 - 25418175

AN - SCOPUS:84908225375

VL - 107

SP - 1939

EP - 1949

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 8

ER -