Dry molten globule-like intermediate during the base-induced unfolding of a multidomain protein

TitleDry molten globule-like intermediate during the base-induced unfolding of a multidomain protein
Publication TypeJournal Article
Year of Publication2017
AuthorsAcharya, N, Mishra, P, Jha, SKumar
JournalPhysical Chemistry Chemical Physics
Volume19
Issue44
Pagination30207-30216
Date PublishedNOV
Type of ArticleArticle
Abstract

The nature of the initial structural events during the base-induced unfolding of the native (N) state of proteins is poorly understood. Combining site-specific fluorescence resonance energy transfer, size exclusion chromatography, dynamic fluorescence quenching, red-edge excitation shift and circular dichroism spectroscopy, we show here that an early intermediate during the base-induced unfolding of a multidomain protein, i.e., the B form, has features of a dry molten globule. We show that the N (sic) B transition involves protein expansion and loosening of packing of inter-domain helices near domains I and II without the disruption of intra-domain packing or any change in hydration of the inter-domain region which resembles a molten hydrocarbon. Surprisingly, the disruption of inter-domain packing accounts for 40-45% of the total change in free energy of complete unfolding. Our results show that the disruption of van der Waals packing can be decoupled in different regions of a protein and could occur prior to hydrophobic solvation during base-induced unfolding, challenging the existing notion.

DOI10.1039/c7cp06614g
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

4.449

Divison category: 
Physical and Materials Chemistry