title: Investigation of DMSO-induced conformational transitions in human serum albumin using two-dimensional raman optical activity spectroscopy.
abstract: Recent Raman and Raman optical activity (ROA) results have demonstrated that dimethyl sulfoxide (DMSO) induces the selective conversion of α-helix motifs into the poly(L-proline) II (PPII) helix conformation in an array of proteins, while β-sheets remain mostly unaffected. Human serum albumin (HSA), a highly α-helical protein, underwent the most dramatic changes and, therefore, was selected as a model for further investigations into the mechanism of this conformational change. Herein we report the use of two-dimensional ROA correlation analysis applying synchronous, autocorrelation, and moving windows approaches in order to understand the conformational transitions in HSA as a function of DMSO concentration. Our results indicate that the destabilization of native α-helix starts at DMSO concentrations as little as 20% in water (v/v), with the transition to PPII helix being complete at ~80% DMSO. These results clearly indicate that any protein preparation containing relatively low concentrations of DMSO should consider possible disruptions in α-helical domains.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Univ. Estadual Paulista - UNESP, Araraquara, Brazil; Manchester Institute of Biotechnology and Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Andrea N L
authors.initials: AN
authors.lastname: Batista
authors.forename: João M
authors.initials: JM
authors.lastname: Batista
authors.forename: Lorna
authors.initials: L
authors.lastname: Ashton
authors.forename: Vanderlan S
authors.initials: VS
authors.lastname: Bolzani
authors.forename: Maysa
authors.initials: M
authors.lastname: Furlan
authors.forename: Ewan W
authors.initials: EW
authors.lastname: Blanch
mesh_terms: D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D006801:Humans; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D012709:Serum Albumin; D004121:Dimethyl Sulfoxide
keywords: 2DCOS; HSA; PPII helix; ROA; moving windows; protein; secondary structure