1gwq
From Proteopedia
| Line 5: | Line 5: | ||
==Overview== | ==Overview== | ||
| - | 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 ... | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1GWQ is a | + | 1GWQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZTW as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: ZWA. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GWQ OCA]. |
==Reference== | ==Reference== | ||
| Line 33: | Line 33: | ||
[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:35:54 2007'' |
Revision as of 10:30, 5 November 2007
|
HUMAN OESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH RALOXIFENE CORE AND TIF2 NRBOX2 PEPTIDE
Overview
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.
About this Structure
1GWQ is a Protein complex structure of sequences from Homo sapiens with ZTW as ligand. Structure known Active Site: ZWA. Full crystallographic information is available from OCA.
Reference
Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha., Warnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC, J Biol Chem. 2002 Jun 14;277(24):21862-8. Epub 2002 Apr 5. PMID:11937504
Page seeded by OCA on Mon Nov 5 12:35:54 2007
Categories: Homo sapiens | Protein complex | Brzozowski, A.M. | Pike, A.C.W. | ZTW | Activator | Af2 coactivator | Agonist | Alternative splicin | Dna-binding | Nuclear protein | Nuclear receptor | Phosphorylation | Polymorphism | Receptor | Ster binding | Transactivation | Transcripti regulation | Transcription factor | Zinc finger
