From steroid receptors to cytokines: The thermodynamics of self-associating systems

Since 1987, the Gibbs Conference on Biothermodynamics has maintained a focus on understanding the quantitative aspects of gene regulatory systems. These studies coupled rigorous techniques with exact theory to dissect the linked reactions associated with bacterial and lower eukaryotic gene regulation. However, only in the last ten years has it become possible to apply this approach to clinically relevant, human gene regulatory systems. Here we summarize our work on the thermodynamics of human steroid receptors and their interactions with multi-site promoter sequences, highlighting results not available from more traditional biochemical and structural approaches. Noting that the Gibbs Conference has also served as a vehicle to promote the broader use of thermodynamics in understanding biology, we then discuss collaborative work on the hydrodynamics of a cytokine implicated in tumor suppression, prostate derived factor (PDF).

Graphical abstractDownload full-size imageHighlights► First thermodynamic dissection of multiple steroid receptor family members. ► Cooperative promoter binding and dimerization are thermodynamically linked. ► This linkage may serve as the basis for receptor-specific gene regulation. ► Cooperativity is tunable via promoter architecture and Na+ concentration. ► Cytokine hydrodynamics reveal structural properties undetected by crystallography.