Title
On the DMSO-dissolved state of insulin : a vibrational spectroscopic study of structural disorder
Author
Faculty/Department
Faculty of Sciences. Chemistry
Publication type
article
Publication
Washington, D.C. ,
Subject
Chemistry
Source (journal)
The journal of physical chemistry : B : condensed matter, materials, surfaces, interfaces and biophysical. - Washington, D.C.
Volume/pages
116(2012) :39 , p. 11863-11871
ISSN
1520-6106
1520-5207
ISI
000309375500009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Upon dissolving in dimethyl sulfoxide (DMSO), native insulin and insulin amyloid fibrils convert into an identical disordered structural state based on IR spectral characteristics. Here, we investigate the DMSO-denatured state of insulin using a number of spectroscopic methods: near-UV circular dichroism, infrared absorption spectroscopy, vibrational circular dichroism (VCD), Raman scattering, and Raman optical activity (ROA), as well as by carrying out 140-ns-long molecular dynamics (MD) simulations of DMSO-dissolved native insulin monomers. According to this work, the DMSO-solvated state of insulin is an ensemble of conformations including polyproline II-type helix and possibly a residual a-helical structure. Effects of DMSO-specific solvation and conformation-restricting covalent structure of insulin (including the three intact disulfide bridges) are argued to play important roles in stabilizing the disordered state of the protein. A comparison of ROA spectra of insulin dissolved in fully deuterated and nondeuterated DMSO suggested transfer of chirality from the protein to the otherwise ROA-silent solvent. Our study provides an example of a biological protein that acquires a substantial population of PP II conformation in an entirely nonaqueous environment. The DMSO-unfolded state of insulin and its dynamics are also discussed in the context of the established link between PP II conformation and protein misfolding.
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