PDBsum entry: 1lo1

Hormone/growth factor receptor/DNA

PDB id: 1lo1

Contents

Protein chain

90 a.a. *

DNA/RNA

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1lo1

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

Date:

05-May-02 Release date: 22-Apr-03

Protein chain

O95718  (ERR2_HUMAN) -  Steroid hormone receptor ERR2

Seq: 500 a.a.

Struc: 90 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: DNA binding (5 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.

ABSTRACT

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.