cover illustration The human pregnane X receptor (PXR) ligand-binding domain (LBD) has been tethered via a flexible peptide linker to a core peptide derived from the coactivator SRC-1. Coactivator-bound receptor was shown to be readily overexpressed in bacteria, purified, stable, and competent to bind known agonist ligands such as SR-12813. This enabled creation of a robust PXR-LBD ligand-binding assay and supporting high-resolution structural studies. The cover figure illustrates that the coactivator peptide (yellow ribbon and carbon atoms) is well-ordered and bound to PXR-LBD (green ribbon and carbon atoms). The flexible linker, present between residues 432 and 444 of the tethered protein sequence, is not observed in the electron density (maroon mesh). The interpretable portions of the tethered protein structure match closely the SR-12813- bound noncovalent complex between PXR-LBD and the coactivator peptide (PDB code 1nrl;Watkins et al. (2003) J. Mol. Biol. 331: 815-828). For further details, please see Wang et al., pp. 425-433.
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