Molten globule intermediates of human serum albumin in low concentration of urea

Abstract

318-324Interaction of non-electrolytes such as urea with proteins especially at lower concentrations is opening-up newer concepts in the understanding of protein stability and folding in proteomics. In this study, the secondary and tertiary structural characteristics and thermal stability of human serum albumin at lower concentrations of urea have been monitored. The protein attains a molten globule like structure at concentration urea be low 2M. This structural state also shows an increase in the α-helical content as compared to the native state. At concentrations of urea above 2M, human serum albumin starts unfolding, resulting in a three-state transition with two mid points of transitions at around 4M and 7M urea concentrations. The characteristics of the partially folded intermediates are discussed with respect to the three component system analyses. Preferential hydration dominates over preferential interaction at lower concentration of urea (up to 2.5M) and at higher concentration, the preferential interaction overtakes preferential hydration in a competitive manner. Formation of structural intermediates at lower concentration of urea is hypothesized as a general phenomenon in proteins and fits in with the observation with preferential interaction parameters by Timasheff and co-workers in the case of Iysozyme and ribonuclease at different <i style="mso-bidi-font-style: normal">pH values