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The structure and structural properties of nuclear receptors is described focusing on the ligand-binding and DNA binding domains and unstructured N-terminal regions. To emphasize the allosteric interdependence among these subunits, a more detailed inspection of the structural properties of the human progesterone receptor is presented.

A quantitative analysis of progesterone receptor (PR)-B self-association energetics is conducted. The studies highlight questions about the relative roles of monomer and dimer in PR-dependent biological function and may additionally offer insight into the mechanisms by which closely related steroid receptors generate transcriptional diversity.

The molecular origins responsible for cooperative DNA binding by the two isoforms of human progesterone receptor (PR-A and PR-B) which could be activated or repressed with Na(+) and K(+) are reported. PR self-association and DNA-dependent cooperativity that are linked to a monovalent cation binding, a binding coupled to modulation of receptor structure suggested functional role of K(+) and Na(+) as allosteric effectors of PR function and physiological regulators of PR action.

The role of progesterone receptor A-isoform (PR-A) in DNA mediating promoter-dependent recruitment of the coactivator, SRC2 is demonstrated. The finding suggests that increased coactivator levels stabilize a higher-order receptor-promoter complex.

The thermodynamic analysis of the interactions of the progesterone (PR) B-isoform (PR-B) with promoters containing either one or two progesterone response elements (PREs) is reported. The results have shown that the cooperative PR-B binding affinity is heavily penalized due to structural alterations in the protein and/or DNA.