Ricerc@Sapienza

Human Serum Albumin (HSA), the most abundant protein of body fluids, has a “modular” three-domain structure potentially responding to stress by means of changes of conformation (1). Besides acting as the main carrier protein of the circulation, HSA is also an obvious target of extracellular reactive oxidant species due to its high abundance in plasma. It is for this reason considered the main anti-oxidant defense in blood (2).
This study was aimed at correlating oxidant-induced chemical and structural effects on HSA. The experiments benefited from the use of a multi-technique instrumental platform which combined the simultaneous collection of SAXS, UV-vis absorbance spectra and fluorescence emission on the same sample volume (3).
Despite the chemical modification, the native shape was preserved up to oxidant/HSA molar ratio < 80, above which a structural transition occurred in the critical oxidant/HSA molar ratio range between 80-120. This conformational variation involved the drifting of one of the end-domains from the rest of the protein and corresponded to the loss of one third of the alpha-helix and a net increase of the protein negative charge. The high reproducibility and well-defined nature of this transition suggested that it represents a structural response characteristic of this multi-domain protein that was never observed before (4).
The ability to tolerate high levels of chemical modification in a folded or only partially unfolded state, as well as the stability to aggregation, provides albumin with optimal features as a biological buffer for the local formation of oxidants.