A relationship between the aggregation rates of α-synuclein variants and the β-sheet populations in their monomeric forms
Articolo
Data di Pubblicazione:
2013
Citazione:
A relationship between the aggregation rates of α-synuclein variants and the β-sheet populations in their monomeric forms / C. Camilloni, M. Vendruscolo. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 117:37(2013), pp. 10737-10741. [10.1021/jp405614j]
Abstract:
Intrinsically disordered proteins constitute a significant part of the human proteome and carry out a wide range of different functions, including in particular signaling and regulation. Several of these proteins are vulnerable to aggregation, and their aberrant assemblies have been associated with a variety of neurodegenerative and systemic diseases. It remains unclear, however, the extent to which the conformational properties of intrinsically disordered proteins in their monomeric states influence the aggregation behavior of these molecules. Here we report a relationship between aggregation rates and secondary structure populations in the soluble monomeric states of a series of mutational variants of α-synuclein. Overall, we found a correlation of over 90% between the changes in β-sheet populations calculated from NMR chemical shift data and the changes in aggregation rates for eight human-to-mouse chimeric mutants. These results provide support to the idea of investigating therapeutic strategies based on the stabilization of the monomeric form of intrinsically disordered proteins through the alteration of their conformational properties.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Humans; Mice; Models, Molecular; Mutation; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Secondary; Recombinant Proteins; alpha-Synuclein; beta-Synuclein; Physical and Theoretical Chemistry; Materials Chemistry2506 Metals and Alloys; Surfaces, Coatings and Films
Elenco autori:
C. Camilloni, M. Vendruscolo
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