Figure 10. Molecular mechanisms underlying context-dependent activities of SLiMs in protein–protein interactions.
The Hox protein is represented as containing a globular structured domain together with two different SLiMs embedded in a disordered region, as indicated. This protein will present different interaction properties with a set of cofactors that could vary depending on the cell context considered. Preferential interactions between cofactors and the protein domain and SLiMs are represented by a colour code. Black bars symbolize the various levels of interaction affinity. In the cell context 1, cofactors are recruited through specific interactions with the globular domain and the two SLiMs. In the cell context 2, there is a supplementary triangular cofactor that displays higher affinity with the red SLiM than the square cofactor. As a consequence, interaction will occur with this triangular (hiding) cofactor, which forbids the interaction with the other SLiM. In this context, the red SLiM behaves as an inhibitory interaction motif. In the cell context 3, post-translational modifications in the disordered region (yellow stars) allow the inhibitory SLiM to establish interactions in cis with the globular domain. These intra-molecular contacts forbid the binding of the other cofactors. The last two mechanisms illustrate how the inhibitory activity of SLiMs could help in distinguishing/specifying interactomes with an identical set of cofactors.