Le Labex Dynamo
2019 Gnutt et al.
Stability Effect of Quinary Interactions Reversed by Single Point Mutations.
Gnutt et al., 2019
In cells, proteins are embedded in a crowded environment that controls their properties via manifold avenues including weak protein-macromolecule interactions. A molecular level understanding of these quinary interactions and their contribution to protein stability, function, and localization in the cell is central to modern structural biology. Using a mutational analysis to quantify the energetic contributions of single amino acids to the stability of the ALS relates protein superoxide dismutase I (SOD1) in mammalian cells, we show that quinary interactions destabilize SOD1 by a similair energetic offset for most of the mutants, but there are notable exceptions: Mutants that alter its surface properties can even lead to a stablization of the protein in the cell as compared to the test tube. In conclusion, quinary interactions can amplify and even reverse the mutational response of proteins, being a key aspect in pathogenic protein misfolding and aggregation.
Publié le : 11/02/2019