Cells are dependent on the ability to adapt to changes in their internal and external environment in order to maintain homeostasis. Fast and efficient regulation of complex signalling cascades is mediated by cellular hub proteins that integrate cellular responses of many different origins. Many hub proteins carry out their hub functionality through interactions with intrinsically disordered proteins (IDPs), or are IDPs themselves, however, the biophysical determinants underlying selectivity and discrimination between different partners are not well-understood. The scope of this thesis work was to improve our understanding of the biophysical characteristics underlying cellular hub function. To this end the folded hub protein Radical-Induced Cell Death1 (RCD1), which interacts with many different intrinsically disordered transcription factors (TFs) through its C-terminal RST domain, was investigated. A common RCD1-RST interacting motif (DE)X(1,2)(YF)X(1,4)(DE)(LIFM V) was identified in the majority of the known TF interaction partners, and it was shown that the motif is conserved all the way back to the emergence of land plants more than 480 million years ago. The motif could readily be used to predict the RCD1 interacting region of known RCD1 binders and the motif was used to identify >100 putative TF partners from different families. Through a combination of NMR and data-driven modelling the structure of RCD1-RST in complex with TF interaction partner DehydrationResponsive-Element 2A (DREB2A) is provided. RCD1-RST forms a four-helix fold containing an open hydrophobic pocket, which constitutes the binding site of DREB2A. NMR data suggested that RCD1-RST is highly dynamic and undergoes global unfolding events of potential importance for partner binding. Based on the structure of RCD1-RST a new domain family, the ααh ubs, was defined. The αα-hubs share structural similarities and are allpresent in proteins the act as central hubs in transcriptional networks. The domains are dynamic and have low conformational stability, which is likely to have implications for adaptation to partners that bind using different anchor points or topologies. In conclusion, this work provides insights to hub functionality and their interactions with IDPs and creates a foundation for future w