Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
Michele Vendruscolo
University of Cambridge, UK
Posters-Accepted Abstracts: J Proteomics Bioinform
I will discuss the extent to which the solubility of proteins can be predicted from the physico-chemical properties of their amino acid sequences. By exploiting the recent availability of proteome-wide mass spectrometry measurements of protein abundance levels, I will then illustrate how these protein solubility predictions can provide insights into the mechanisms of protein homeostasis. An important principle that has emerged from these studies is the �life on the edge hypothesis�, according to which in living systems proteins are expressed at levels close to their solubility limits. This finding implies that the concentrations of proteins are often close to their critical values and thus that these molecules are constantly in danger of aggregation. Investigation of the consequences of this idea has recently resulted in the discovery that the native states of proteins are kinetically but not thermodynamically stable under many conditions, thus modifying very significantly one of the major principles on which protein science is based that is the native states of proteins are global minima on their free energy landscapes under physiological conditions. This result has profound implications in molecular biology and medicine as the fact that proteins are only marginally soluble in the cell makes them vulnerable to aggregation under stress conditions or as a consequence of other changes such as those associated with ageing.
Email: mv245@cam.ac.uk