PDBsum entry 1lo1

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protein dna_rna metals links
Hormone/growth factor receptor/DNA PDB id
Protein chain
90 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Hormone/growth factor receptor/DNA
Title: Estrogen related receptor 2 DNA binding domain in complex with DNA
Structure: Steroid hormone receptor err2. Chain: a. Fragment: DNA binding domain. Synonym: err-beta, estrogen receptor-like 2, estrogen- related receptor,beta. Engineered: yes. Mutation: yes. 5'-d( Gp Cp Tp Cp Ap Ap Gp Gp Tp Cp Ap Cp G)-3'. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: herr2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic: yes
NMR struc: 20 models
Authors: M.D.Gearhart,S.M.A.Holmbeck,R.M.Evans,H.J.Dyson,P.E.Wright
Key ref:
M.D.Gearhart et al. (2003). Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition. J Mol Biol, 327, 819-832. PubMed id: 12654265 DOI: 10.1016/S0022-2836(03)00183-9
05-May-02     Release date:   22-Apr-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O95718  (ERR2_HUMAN) -  Steroid hormone receptor ERR2
508 a.a.
90 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     sequence-specific DNA binding transcription factor activity     4 terms  


DOI no: 10.1016/S0022-2836(03)00183-9 J Mol Biol 327:819-832 (2003)
PubMed id: 12654265  
Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition.
M.D.Gearhart, S.M.Holmbeck, R.M.Evans, H.J.Dyson, P.E.Wright.
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.
  Selected figure(s)  
Figure 3.
Figure 3. Solution structure of the hERR2-DNA complex. (A) Stereo view of the backbone trace of superposition of the ensemble of 20 NMR structures of the hERR2-DNA complex, including the core DBD (blue) and the CTE (pink), with a schematic representation of the DNA (gray). Residues 187-194 are omitted for clarity. The zinc atoms are shown as green spheres. DNA bases that make major-groove interactions with the protein are colored blue, and those that make minor-groove interactions are colored pink. (B) Stereo view of a ribbon diagram of a representative structure from the ensemble. Color scheme as in (A). The side-chain of Tyr185 is shown.
Figure 5.
Figure 5. A hydrophobic interaction is formed between residues in the CTE and the core DBD upon complex formation with DNA. The core DBD and the modified AT-hook motif are shown as a molecular surface colored according to electrostatic potential. The blue patches at either end of the modified AT-hook motif correspond to the positively charged guanidinium groups of Arg179 and Arg182. The surface has been removed from Gln183 to Lys186 to show the interaction between Tyr185 and a hydrophobic patch on the core DBD formed primarily by Val117 and Leu169. A stick representation of the DNA is shown in green.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 819-832) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19553667 K.K.Hill, S.C.Roemer, D.N.Jones, M.E.Churchill, and D.P.Edwards (2009).
A progesterone receptor co-activator (JDP2) mediates activity through interaction with residues in the carboxyl-terminal extension of the DNA binding domain.
  J Biol Chem, 284, 24415-24424.  
19865164 R.Rohs, S.M.West, A.Sosinsky, P.Liu, R.S.Mann, and B.Honig (2009).
The role of DNA shape in protein-DNA recognition.
  Nature, 461, 1248-1253.  
18662995 D.L.van den Berg, W.Zhang, A.Yates, E.Engelen, K.Takacs, K.Bezstarosti, J.Demmers, I.Chambers, and R.A.Poot (2008).
Estrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression.
  Mol Cell Biol, 28, 5986-5995.  
18441008 H.Greschik, M.Althage, R.Flaig, Y.Sato, V.Chavant, C.Peluso-Iltis, L.Choulier, P.Cronet, N.Rochel, R.Schüle, P.E.Strömstedt, and D.Moras (2008).
Communication between the ERRalpha homodimer interface and the PGC-1alpha binding surface via the helix 8-9 loop.
  J Biol Chem, 283, 20220-20230.
PDB code: 3d24
18838537 L.A.Campbell, E.J.Faivre, M.D.Show, J.G.Ingraham, J.Flinders, J.D.Gross, and H.A.Ingraham (2008).
Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).
  Mol Cell Biol, 28, 7476-7486.  
18474528 S.C.Roemer, J.Adelman, M.E.Churchill, and D.P.Edwards (2008).
Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding.
  Nucleic Acids Res, 36, 3655-3666.  
18174917 A.M.Tremblay, and V.Giguère (2007).
The NR3B subgroup: an ovERRview.
  Nucl Recept Signal, 5, e009.  
17137423 D.L.Bain, A.F.Heneghan, K.D.Connaghan-Jones, and M.T.Miura (2007).
Nuclear receptor structure: implications for function.
  Annu Rev Physiol, 69, 201-220.  
17981120 R.Joshi, J.M.Passner, R.Rohs, R.Jain, A.Sosinsky, M.A.Crickmore, V.Jacob, A.K.Aggarwal, B.Honig, and R.S.Mann (2007).
Functional specificity of a Hox protein mediated by the recognition of minor groove structure.
  Cell, 131, 530-543.
PDB codes: 2r5y 2r5z
16920361 C.Crane-Robinson, A.I.Dragan, and P.L.Privalov (2006).
The extended arms of DNA-binding domains: a tale of tails.
  Trends Biochem Sci, 31, 547-552.  
16914190 P.Ascenzi, A.Bocedi, and M.Marino (2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
  Mol Aspects Med, 27, 299-402.  
16931575 S.C.Roemer, D.C.Donham, L.Sherman, V.H.Pon, D.P.Edwards, and M.E.Churchill (2006).
Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.
  Mol Endocrinol, 20, 3042-3052.
PDB code: 2c7a
14739282 V.S.Melvin, C.Harrell, J.S.Adelman, W.L.Kraus, M.Churchill, and D.P.Edwards (2004).
The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB.
  J Biol Chem, 279, 14763-14771.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.