Denaturants such as the guanidinium cation unfold proteins at molar concentrations, which interferes with ultraviolet- and infrared-based spectroscopy measurements. Dodine denatures some proteins cooperatively at a thousand-fold lower concentration, allowing for spectroscopy measurements. Nonetheless, dodine's microscopic mechanism of interaction with proteins is not understood. We probe the effect of dodine on α-helices and tertiary structure by investigating the stability of the small helical protein B. Experiments show that dodine promotes formation of helical structure (a kosmotropic effect), while inducing the loss of tertiary structure (a chaotropic effect). Although dodine destabilizes native protein structure, it does not lower the thermal denaturation midpoint temperature of protein B. All-atom simulations reveal the cause for both observations: The denaturant action of dodine's guanidyl headgroup is counteracted by its aliphatic tail, which stabilizes amphipathic helices and associates with an expanded protein core. The Janus-like behavior of headgroup and tail make dodine a simultaneous stabilizer-destabilizer or "kosmo-chaotrope".
ASJC Scopus subject areas
- Materials Science(all)
- Physical and Theoretical Chemistry