IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
METAL IONS IN SYNUCLEINOPATHIES: AN SPECTROSCOPIC VIEW
Autor/es:
FERNÁNDEZ, CO
Lugar:
Rio de Janeiro, Brasil
Reunión:
Workshop; 11th NMR Users Meeting Workshop: NMR in South America; 2007
Resumen:
Many proteins associated with neurodegenerative diseases (PrP, APP, Ab peptide and SOD-1) have metal binding properties. In the documented examples metal binding relates to pathogenesis via an impact on aggregation or production of oxidative damage. Thus, defining binding sites and the molecular details of complex formation may provide insights into pathogenic processes and neuronal biology. Our objective is to establish the role of metal ions in synucleinopathies at the molecular resolution currently available for other amyloidoses. The interaction of Cu(II) and other divalent metal ions with a-Synuclein (AS) were studied using low and high-resolution spectroscopic techniques.1 The metal-AS interactions were characterized at single-residue resolution by NMR. The influence of metals on inducing AS fibrillation was strongly linked to their binding properties. A comparative analysis reveals a hierarchy in metal binding to AS, dictated by structural factors involving different domains of the protein.1-3 The new insights into the structural basis of metal ion interactions with AS support a tighter link with other amyloid-related disorders such as Alzheimer and prion diseases. 1.Rasia et al, PNAS 2005, 102, 4294; 2.Bertoncini et al, PNAS, 2005, 102, 1430; 3. Binolfi et al, JACS 2006, 128, 9893.