Role of metal ions in the aggregation processes of proteins

In the last years, it has been observed and studied the aggregation process induced by metal ions, for biomedical and biotechnological purposes. The idea arises from the finding that increased metal concentration (mainly copper, iron and zinc) is present in the brains of Alzheimer's disease patients both in the amyloid plaques and in the cortical tissues. Cu²⁺ and Zn²⁺ metal ions have a different physiological role and it has been observed that, in vitro, both promote (zinc more than copper) aggregation in amyloid fibrils and/or in amorphous aggregates. Moreover, as a function of pH and metal concentration, these two ions have shown different behaviours.
The second purpose of scientific interest, in studying aggregation protein process, drops in the field of biotechnologies like the food technology. In fact, most processes in manufacturing of foods are based on thermal treatments. Knowing the structures of the proteins during and after these treatments is extremely important also for allergenic problems. Regarding dairy production, milk proteins are much studied because some of them are the major constituent of fouling deposits in the dairy industry. Metal ions are also able to induce cold gelation and the gel texture formation depends on different parameters as pH conditions and protein and/or iron concentration. Therefore, protein aggregation is important in food processing and it is relevant to know how aggregation of food proteins occurs and if it is a source of amyloid fibrils.

In general, our research activity concerns the study of the conformational changes of secondary and tertiary structures accompanying the aggregation process induced by heating of different model proteins, such as β-Lactoglobulin A, Bovine Serum Albumin, Lysozyme, Insulin, Concanavalin A. In particular, a field of our studies is centred on the effects of the presence of metal ions, such as zinc or copper, on the time evolution of protein aggregation and on the characteristic conformational changes. The research activity is carried out via Static and Dynamic light scattering, characterizing the evolution of the aggregate growth, and via infrared absorption and fluorescence spectroscopy, characterizing the secondary and tertiary structural changes, respectively. AFM was used to known the morphology of the aggregates grown as a consequence of protein heating. Results have shown that metal ions have a crucial role in the time evolution of the aggregation process and in the formation of protein cold-gels, though showing differences at the changing of the metal or the protein.

In the last months, we have also studied the effects of the protein glycation on the evolution of the aggregation process and on simultaneous conformational changes of BSA, having shown that the glycation hinders the aggregate growth up to inhibit it when the protein molecules are wholly glycated.

“Role of the metal ions in the aggregation processes of proteins”, extract from the PRIN 2005 document.

List of related papers

• G. Navarra, M. Leone, V. Militello, Biophys. Chem. 131, (2007) 52-61: "Thermal aggregation of β-Lactoglobulin in presence of metal ions"
• V. Militello G. Navarra, V. Foderà, F. Librizzi, V. Vetri, M. Leone , Review in "Biophysical Inquiry into Protein Aggregation and Amyloid Diseases" (2008) 181-232. Editors P.L. San Biagio and D. Bulone, Transworld Research Network, Kerala, India: "Thermal aggregation of proteins in the presence of metal ions."
• G. Navarra, D. Giacomazza, M. Leone, F. Librizzi, V. Militello and P.L. San Biagio Eur. Biophys. J. 38, (2009) 437-446: "Thermal aggregation and ion-induced cold-gelation of Bovine Serum Albumin"
• G. Navarra, A. Tinti, M. Leone, V. Militello, A. Torreggiani, J. Inorg. Biochem. 103 (2009) 1729-1738: "Influence of metal ions on thermal aggregation of bovine serum albumin: Aggregation kinetics and structural changes"
• P. Rondeau, G. Navarra, F. Cacciabaudo, M. Leone, E. Bourdon, V. Militello, Biochim. Biophys. Acta – Protein & Proteomics 1804, (2010) 789-798: "Thermal aggregation of glycated Bovine Serum Albumin."