Specificity of MYB interactions relies on motifs in ordered and disordered contexts

Millard PS, Weber K, Kragelund BB, Burow M
Nucleic Acids Res. 2019 Aug 10, doi: 10.1093/nar/gkz691

In higher plants, MYB and basic helix-loop-helix (bHLH) transcription factors constitute the two most abundant TF families, each containing more than a hundred members in Arabidopsis thaliana. Physical interactions between members of these two transcription factor families regulate many important biological processes. For most of these highly specific interactions, the features involved are not well understood.

We identified the motif mediating interaction between MYB TFs from subgroup 12 and their bHLH partners. Unlike other known MYB-bHLH interactions, the motif locates to the center of the predicted disordered non-MYB region. We characterized the core motif, which enabled accurate prediction of previously unknown bHLH-interacting MYB TFs in Arabidopsis thaliana. We also confirmed the functional importance of this Short Linear Motif (SLiM) in planta.

SLiMs have distinctive features in terms of their interaction interfaces and evolution, compared to their counterparts in globular domain interactions and are common in intrinsically disordered regions of regulatory proteins and transcription factors. The identification of this interaction motif outside the structured DNA-binding domain suggests that MYB-bHLH interactions must have arisen independently multiple times.