Orphan nuclear receptors adopted by crystallography.
Of the large nuclear hormone receptor superfamily of proteins, orphan nuclear receptors have remained a mystery owing to their lack of identified ligands and their constitutive nature. Now, structures of several ligand-binding domains of orphan receptors have provided some surprising insights that were not anticipated from molecular studies. Therefore, most orphan nuclear receptors have now been 'adopted' and their regulation has been shown to range from true ligand-independence to highly promiscuous ligand-dependence. Former orphan receptors have been found to contain ligand-binding pockets that range in volume from vast (>1600A3) to non-existent and have been shown to generate surface AF2 motifs that range from being multifunctionally active to distinctly inactive. Insights from these new structures illustrate how powerful a structural biology approach can be when integrated with molecular and cellular physiology.
Ingraham
Holly A
HA
Department of Physiology, 1550 4(th) Street, University of California, San Francisco, Box 2611, Mission Bay Campus, San Francisco, CA 94143-2611, USA. holly.ingraham@ucsf.edu
Redinbo
Matthew R
MR
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D000077297:Pregnane X Receptor; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008024:Ligands; C539821:NR4A1 protein, human; C082631:NR5A2 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors