Effects of intermediates on aggregation of native bovine serum albumin

Protein aggregation has been recognized to be a pathological indicator for several fatal diseases, such as Alzheimer's disease, transmissible spongifo rm encephalopathies, Creutzfeldt-Jacob disease, etc. Aggregation usually in volves conformational changes of proteins that have acquired an intermediat e p-structure-rich conformation and can occur even at low protein concentra tion. Recent work in our laboratory has shown that bovine serum albumin (BS A), even at low-concentration, exhibits self-association properties related to conformational changes, so providing a very convenient model system to study this class of problems. Here we report data (obtained by different ex perimental techniques) on a mixture of BSA in native and intermediate (p-st ructure-rich) form. Results show that the interaction between the two speci es is responsible for a decrease in the thermodynamic stability of the solu tion. This occurs without requiring noticeable conformational changes of th e native protein. Results presented here can provide new insight on the 'pr otein only' hypothesis proposed for the formation of plaques involved in se veral neurodegenerative diseases. (C) 2001 Elsevier Science B.V. All rights reserved.