Role of conformational dynamics and flexibilities in the steroid receptor-coregulator protein complex formation

Understanding of the mechanisms of actions of the steroid hormone receptor (SHR)-coregulator (CoR) protein complexes in the gene regulations has revolutionized the field of molecular endocrinology and endocrine-related oncology. The discovery and characterization of steroid receptor coactivators (SRCs) and their ability to bind various transcription factors including SHRs to coordinate the regulation of multiple target genes highlights their importance as key coregulators in various cellular signaling crosstalks as well as therapeutic target for various endocrine-related disorders specifically endocrine cancers. The dynamic nature of the SHR-CoR multi-protein complexes indicate the critical role of conformational flexibilities within specific protein(s). In recent years, the importance of conformational dynamics of the SHRs in the intramolecular and intermolecular allosteric regulations mediated via their intrinsically disordered (ID) surfaces has been highlighted. In this review article, we have discussed the importance of ID conformations within the SRCs that may also be playing an important role in the formation/deformation of multi protein complexes involving SHRs and CoRs and subsequent target gene regulation.