Influence of metal ions on thermal aggregation of bovine serum albumin: aggregation kinetics and structural changes.
Metal ions are implicated in protein aggregation processes of several neurodegenerative pathologies. In this work the effects of Cu(II) and Zn(II) ions on heat-induced structural modifications of bovine serum albumin (BSA) were studied, with the aim of delineating the role of these ions in the early stages of proteins aggregation kinetics. A joint application of different techniques was used. The aggregate growth was followed by dynamic light scattering measurements, whereas the conformational changes occurring in the protein structure were monitored by Raman and IR spectroscopy. Both in absence and in presence of metal ions, heating treatment gave rise to beta-structures to the detriment of alpha-helix conformation of BSA. The temperature of protein unfolding was not sensitively affected by the presence of Zn(II) or Cu(II) ions; on the contrary, only Zn(II) ions slightly promoted the heat-induced aggregation of the protein, since bigger aggregates were formed in their presence. The different efficacy of the Cu(II) and Zn(II) ions in promoting the BSA aggregation were highlighted by Raman measurements, assessing the role of His residues in metal binding. A distinct polypeptide folding of the two metal-BSA systems takes place, since the predominant mode of metal binding depends on metal. In particular, in Zn-BSA the metal coordination involves the imidazole N(tau) atom of His which can promote inter-molecular cross-linking.
Navarra
Giovanna
G
Dipartimento di Scienze Fisiche ed Astronomiche, Università di Palermo and CNISM, 90123 Palermo, Italy.
Tinti
Anna
A
Leone
Maurizio
M
Militello
Valeria
V
Torreggiani
Armida
A
D000818:Animals; D002417:Cattle; D003300:Copper / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D007700:Kinetics; D011485:Protein Binding; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D015032:Zinc / Q000378:metabolism*
D012710:Serum Albumin, Bovine; D006639:Histidine; D003300:Copper; D015032:Zinc