Authors: N. El Kadi, N. Taulier, W. Urbach, M. Waks
Affilation: Paris V, France
Pages: 423 - 426
Keywords: albumin, amphiphiles, adiabatic compressibility, circular dichroïsm, conformational transitions, hydration
Defective folding diseases have emerged in the last decade as prevalent in an ageing population. In this respect any increased knowledge of folding mechanisms could be crucial for preventing, treating or even curing these neurodegenerative processes. In the present work we have used bovine serum albumin (BSA), the most abundant macromolecule in the circulatory system, displaying a reversible conformational transition at low pH. Moreover it is a carrier protein for ligands and more than 70% of commonly administered drugs. The aim of our work is to investigate the correlation existing between the protein conformation and its compressibility measured by an ultrasonic technique developed in the laboratory (LIP). Indeed, variations of partial specific volume and adiabatic compressibility are macroscopic observables, exquisitely sensitive to protein (BSA) hydration and conformational changes (unfolding/ refolding). We have examined the behaviour of BSA during its unfolding and its refolding at low pH, with the help of small neutral molecules called osmolytes. In addition we have studied the binding of amphiphile molecules to the protein. All together, our results demonstrate the very close correlation existing between these methods and circular dichroïsm as well as the precision and the high sensibility of ultrasonic techniques to characterize protein conformational alterations, and ligand binding. They also underline the importance of hydration in protein design, for example of de novo drug carriers, modelled on albumin.