Database Accession: DI2000015
Name: Human estrogen receptor alpha ligand-binding domain in complex with NCOA2 peptide
PDB ID: 1gwq
Experimental method: X-ray (2.45 Å)
Source organism: Homo sapiens
Proof of disorder:
Kd: 7.60×10-08 M
Primary publication of the structure:
Wärnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC
Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha.
(2002) J. Biol. Chem. 277: 21862-8
PMID: 11937504
Abstract:
The activation function 2/ligand-dependent interaction between nuclear receptors and their coregulators is mediated by a short consensus motif, the so-called nuclear receptor (NR) box. Nuclear receptors exhibit distinct preferences for such motifs depending both on the bound ligand and on the NR box sequence. To better understand the structural basis of motif recognition, we characterized the interaction between estrogen receptor alpha and the NR box regions of the p160 coactivator TIF2. We have determined the crystal structures of complexes between the ligand-binding domain of estrogen receptor alpha and 12-mer peptides from the Box B2 and Box B3 regions of TIF2. Surprisingly, the Box B3 module displays an unexpected binding mode that is distinct from the canonical LXXLL interaction observed in other ligand-binding domain/NR box crystal structures. The peptide is shifted along the coactivator binding site in such a way that the interaction motif becomes LXXYL rather than the classical LXXLL. However, analysis of the binding properties of wild type NR box peptides, as well as mutant peptides designed to probe the Box B3 orientation, suggests that the Box B3 peptide primarily adopts the "classical" LXXLL orientation in solution. These results highlight the potential difficulties in interpretation of protein-protein interactions based on co-crystal structures using short peptide motifs.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
RNA polymerase II core promoter proximal region sequence-specific DNA binding Interacting selectively and non-covalently with a sequence of DNA that is in cis with and relatively close to a core promoter for RNA polymerase II.
transcription factor binding Interacting selectively and non-covalently with a transcription factor, any protein required to initiate or regulate transcription.
nuclear hormone receptor binding Interacting selectively and non-covalently with a nuclear hormone receptor, a ligand-dependent receptor found in the nucleus of the cell.
Biological process:
negative regulation of transcription from RNA polymerase II promoter Any process that stops, prevents, or reduces the frequency, rate or extent of transcription from an RNA polymerase II promoter.
transcription, DNA-templated The cellular synthesis of RNA on a template of DNA.
positive regulation of transcription from RNA polymerase II promoter Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
single-multicellular organism process A biological process occurring within a single, multicellular organism.
positive regulation of molecular function Any process that activates or increases the rate or extent of a molecular function, an elemental biological activity occurring at the molecular level, such as catalysis or binding.
regulation of signal transduction Any process that modulates the frequency, rate or extent of signal transduction.
intracellular receptor signaling pathway Any series of molecular signals initiated by a ligand binding to an receptor located within a cell.
cellular response to hormone stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
Cellular component:
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
Structural annotations of the participating protein chains.Entry contents: 3 distinct polypeptide molecules
Chains: C, A, B
Notes: Chain D was removed as chains A, B and C highlight the biologically relevant interaction.
Name: Nuclear receptor coactivator 2
Source organism: Homo sapiens
Length: 9 residues
Sequence:Sequence according to PDB SEQRESKILHRLLQD
UniProtKB AC: Q15596 (positions: 688-696) Coverage: 0.6%
UniRef90 AC: UniRef90_Q61026 (positions: 688-696)
Name: Estrogen receptor
Source organism: Homo sapiens
Length: 248 residues
Sequence:Sequence according to PDB SEQRESSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHR
UniProtKB AC: P03372 (positions: 301-548) Coverage: 41.7%
UniRef90 AC: UniRef90_P03372 (positions: 301-548)
Name: Estrogen receptor
Source organism: Homo sapiens
Length: 248 residues
Sequence:Sequence according to PDB SEQRESSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHR
UniProtKB AC: P03372 (positions: 301-548) Coverage: 41.7%
UniRef90 AC: UniRef90_P03372 (positions: 301-548)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain C:
The protein region involved in the interaction contains a known functional linear motif (LIG_NRBOX).
Chain A:
The nuclear hormone receptor domain involved in the interaction is known to adopt a stable structure in isolation in dimeric form. A solved structure of the domain dimer without bound ligands is represented by PDB ID 1g50.
Chain B:
The nuclear hormone receptor domain involved in the interaction is known to adopt a stable structure in isolation in dimeric form. A solved structure of the domain dimer without bound ligands is represented by PDB ID 1g50.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
Download our modified structure (.pdb)
