Stability, conformational plasticity, oligomerization behaviour and equilibrium unfolding intermediates of the Ebola virus matrix protein VP40

Abstract

In this work, we have analyzed such properties through the thermodynamic characterization of VP40 unfolding equilibrium under different buffered conditions by means of calorimetric and spectroscopic techniques. Multi-functional proteins are usually arranged in different structural domains. The three domains of monomeric streptokinase represent the simplest scenario, where each domain acts as an independent and cooperative structural unit (Azuaga, Dobson, Mateo & Conejero-Lara 2002). Unfortunately, multi-domain proteins rarely present such a simplified scheme of unfolding equilibriums, since the macrostates can be also involved in oligomerization equilibriums, thus displaying a rather complex behaviour upon unfolding. The full thermodynamic characterization of the process typically becomes rather challenging in these cases. Nonetheless, the conformational and energetic information derived from these intricate equilibriums is essential to understand, not only the folding plasticity and stability, but also the functionalities of these multi-domain proteins (Privalov 1982). Despite the complex behaviour observed, we have been able to obtain a complete thermodynamic analysis of the thermal unfolding and stability of VP40.