Unfolding and refolding of bovine serum albumin at acid pH: ultrasound and structural studies

Biophys J. 2006 Nov 1;91(9):3397-404. doi: 10.1529/biophysj.106.088963. Epub 2006 Jul 21.

Abstract

Serum albumin is the most abundant protein in the circulatory system. The ability of albumins to undergo a reversible conformational transition, observed with changes in pH, is conserved in distantly related species, suggesting for it a major physiological role possibly related to the transport of small molecules including drugs. We have followed changes of bovine serum albumin (BSA) in volume by densimetry and in adiabatic compressibility during its conformational transition from pH 7-2, using ultrasound measurements. In parallel, circular dichroism was measured. The volume and adiabatic compressibility decrease from pH 4 to 2. The change in ellipticity shows a decrease over the same pH range from 70% to 40% of its alpha-helix content. Sorbitol, at concentrations from 0 to 2 M, led to the progressive restoration of BSA volume and compressibility values, as well as a substantial recovery of its original alpha-helix content. This finding implies that the compressibility variation observed reflects the conformational changes during the transition. The mutual interactions of the mechanical properties and structural features of BSA reported here are important in biotechnology for research in material sciences and for the design and the development of new, tailor-made drug carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Crystallography
  • Hydrogen-Ion Concentration
  • Models, Chemical*
  • Models, Molecular*
  • Pressure
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding
  • Serum Albumin, Bovine / chemistry*
  • Serum Albumin, Bovine / ultrastructure*
  • Sorbitol / chemistry*
  • Ultrasonography

Substances

  • Serum Albumin, Bovine
  • Sorbitol