Editor’s summary
Globular proteins typically have a stable and densely packed core. Whether mutations are detrimental thus depends on context, and one residue change can potentially be mitigated by another. Escobedo et al. systematically randomized a small set of hydrophobic residues in the cores of three well-studied globular proteins and evaluated the effects on stability and partner binding. There were many possible core residue combinations that retained thermal stability, and a simple energetic model was trained to predict functional cores. This work helps to demystify allosteric interactions in protein structure and lends support to efforts to engineer surface and core sequences.
2 Likes
Cool stuff.
But when applying this to the big picture, it’s important to remember that globular proteins are not representative, as they are far more stable than typical proteins. On top of that, “well-studied” almost always means that they are easy to express in heterologous systems, making them even less representative of typical globular proteins, much less proteins in general.
1 Like
This topic was automatically closed 7 days after the last reply. New replies are no longer allowed.