Archives of Biochemistry and Biophysics 2005-03-01

Molecular mechanism of the inhibition of cytochrome c aggregation by Phe-Gly.

Carmelo La Rosa, Danilo Milardi, Emanuela Amato, Matteo Pappalardo, Domenico Grasso

Index: Arch. Biochem. Biophys. 435(1) , 182-9, (2005)

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Abstract

Experimental and computational studies suggest that few general principles govern protein/protein interactions and aggregation. The knowledge of these rules may be exploited to design peptides that are able to interfere with the self-assembly and aggregation of proteins. This work is aimed to verify the validity of this hypothesis by investigating the interaction of cytochrome c with Phe and Gly amino acids, Ala-His (carnosine), and two water-soluble dipeptides Phe-Gly and Gly-Phe. The combined use of (1)H NMR, MD, and DSC has shown that: (i) at neutral pH, only Phe-Gly is able to prevent the thermally induced aggregation of cytochrome c; (ii) Phe-Gly interacts with Gly45 and Phe46 residues of the protein, either when the protein is in the folded or in the unfolded state; and (iii) the interaction of Phe-Gly with cytochrome c is sequence-dependent. These results support the hypothesis that the basic principles that describe protein aggregation can be used for the design of peptides with antiaggregating properties.