Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition.
While most nuclear receptors bind DNA as homo or heterodimers, the human estrogen related receptors (hERRs) are members of a subfamily of orphan receptors that bind DNA as monomers. We have determined the solution structure of the DNA binding domain (DBD) of hERR2 bound to its cognate DNA. The structure and base interactions of the core DBD are similar to those of other nuclear receptors. However, high-affinity, sequence-specific DNA binding as a monomer necessitates formation of additional base contacts outside the core DBD. This is accomplished using a modified guanosine-binding "AT-hook" within the C-terminal extension (CTE) flanking the DBD, which makes base-specific minor groove interactions. The structure of the CTE is stabilized both by interactions with the DNA and by packing against a region of the core DBD normally reserved for dimerization. This pseudo-dimer interface provides a basis for the expansion of DNA recognition and suggests a mechanism through which dimerization may have evolved from an ancestral monomeric receptor.
Gearhart
Micah D
MD
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Holmbeck
Signe M A
SM
Evans
Ronald M
RM
Dyson
H Jane
HJ
Wright
Peter E
PE
D000595:Amino Acid Sequence; D020029:Base Pairing; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D006151:Guanosine / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000737:chemistry; D017354:Point Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers
C490918:ESRRB protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D006151:Guanosine; D004247:DNA; D010100:Oxygen