In a very recent PNAS, J. Danielsson et al. [see here] present a very interesting work focusing on protein stability in cell. They used in-cell NMR to reconstruct the stability curve of the protein SOD1. The interesting finding is that when the protein is moved in two different types of cells, a bacterial (E. coli) and a mammalian cell (A2780) the protein is destabilised in both cases. Firstly, this finding questions the common believe that under crowding a protein gets stabilised because of an excluded volume effect. In short, if the available space is reduced because of the presence of a large numbers of macromolecules acting as crowders, the highly entropic and extended unfolded state should be unfavored. This picture is however very simplified since in both folded and unfolded states, a targeted protein interacts with its neighbours, and the results of these specific interactions, i.e. electrostatic, could alter the equilibrium favouring unfolding. The effect of different specific interactions, is actually probed by the authors, showing that by changing the local environment, moving from E.coli to a mammalian cell, the destabilisation effect is different. Last, but not least, the destabilisation results as an increase of the specific heat of unfolding that shrinks the stability curve. This calls for a particular effect of the crowders on the nature of the unfolded state. Stay tune, because the life of proteins in cell is where our interest is going....
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| Molecular view of molecular crowding. Project at the Riken HPC center, Japan [see here] |
