3d24
From Proteopedia
(New page: '''Unreleased structure''' The entry 3d24 is ON HOLD Authors: Moras, D., Greschik, H., Flaig, R., Sato, Y., Rochel, N., Structural Proteomics in Europe (SPINE) Description: Crystal str...) |
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| + | {{STRUCTURE_3d24| PDB=3d24 | SCENE= }} | ||
| - | + | '''Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha)''' | |
| - | Description: Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha) | ||
| + | ==Overview== | ||
| + | While structural studies on the ligand-binding domain (LBD) have established the general mode of nuclear receptor (NR)-coactivator interaction, determinants of binding specificity are only partially understood. The LBD of estrogen receptor (ER) alpha, for example, interacts only with a region of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha that contains the canonical LXXLL motif (NR box2), whereas the LBD of estrogen-related receptor (ERR)alpha binds also efficiently an untypical, LXXYL-containing region (NR box3) of PGC-1alpha. Surprisingly, in a previous structural study, the ERalpha LBD has been observed to bind NR box3 of transcriptional intermediary factor (TIF)-2 untypically via LXXYL, while the ERRalpha LBD binds this region of TIF-2 only poorly. Here we present a new crystal structure of the ERRalpha LBD in complex with a PGC-1alpha box3 peptide. In this structure, residues N-terminal of the PGC-1alpha LXXYL motif form contacts with helix 4, the loop connecting helices 8 and 9, and with the C-terminus of the ERRalpha LBD. Interaction studies using wild-type and mutant PGC-1alpha and ERRalpha show that these contacts are functionally relevant and required for efficient ERRalpha/PGC-1alpha interaction. Furthermore, a structure comparison between ERRalpha and ERalpha and mutation analyses provide evidence that the helix 8-9 loop, which differs significantly in both nuclear receptors, is a major determinant of coactivator binding specificity. Finally, our results reveal that in ERRalpha the helix 8-9 loop allosterically links the LBD homodimer interface with the coactivator cleft, thus providing a plausible explanation for distinct PGC-1alpha binding to ERRalpha monomers and homodimers. | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 | + | ==About this Structure== |
| + | 3D24 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D24 OCA]. | ||
| + | |||
| + | ==Reference== | ||
| + | Communication between the ERR alpha homodimer interface and the PGC-1alpha binding surface vie the helix 8-9 loop., Greschik H, Althage M, Flaig R, Sato Y, Peluso-Iltis C, Chavant V, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D, J Biol Chem. 2008 Apr 25;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18441008 18441008] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Protein complex]] | ||
| + | [[Category: Flaig, R.]] | ||
| + | [[Category: Greschik, H.]] | ||
| + | [[Category: Moras, D.]] | ||
| + | [[Category: Rochel, N.]] | ||
| + | [[Category: SPINE, Structural Proteomics in Europe.]] | ||
| + | [[Category: Sato, Y.]] | ||
| + | [[Category: Coactivator]] | ||
| + | [[Category: Dna-binding]] | ||
| + | [[Category: Ligand binding domain]] | ||
| + | [[Category: Metal-binding]] | ||
| + | [[Category: Nuclear receptor]] | ||
| + | [[Category: Nucleus]] | ||
| + | [[Category: Phosphoprotein]] | ||
| + | [[Category: Polymorphism]] | ||
| + | [[Category: Rna-binding]] | ||
| + | [[Category: Spine]] | ||
| + | [[Category: Structural genomic]] | ||
| + | [[Category: Structural proteomics in europe]] | ||
| + | [[Category: Transcription]] | ||
| + | [[Category: Transcription regulation]] | ||
| + | [[Category: Zinc]] | ||
| + | [[Category: Zinc-finger]] | ||
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:50:58 2008'' | ||
Revision as of 07:50, 11 June 2008
Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha)
Overview
While structural studies on the ligand-binding domain (LBD) have established the general mode of nuclear receptor (NR)-coactivator interaction, determinants of binding specificity are only partially understood. The LBD of estrogen receptor (ER) alpha, for example, interacts only with a region of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha that contains the canonical LXXLL motif (NR box2), whereas the LBD of estrogen-related receptor (ERR)alpha binds also efficiently an untypical, LXXYL-containing region (NR box3) of PGC-1alpha. Surprisingly, in a previous structural study, the ERalpha LBD has been observed to bind NR box3 of transcriptional intermediary factor (TIF)-2 untypically via LXXYL, while the ERRalpha LBD binds this region of TIF-2 only poorly. Here we present a new crystal structure of the ERRalpha LBD in complex with a PGC-1alpha box3 peptide. In this structure, residues N-terminal of the PGC-1alpha LXXYL motif form contacts with helix 4, the loop connecting helices 8 and 9, and with the C-terminus of the ERRalpha LBD. Interaction studies using wild-type and mutant PGC-1alpha and ERRalpha show that these contacts are functionally relevant and required for efficient ERRalpha/PGC-1alpha interaction. Furthermore, a structure comparison between ERRalpha and ERalpha and mutation analyses provide evidence that the helix 8-9 loop, which differs significantly in both nuclear receptors, is a major determinant of coactivator binding specificity. Finally, our results reveal that in ERRalpha the helix 8-9 loop allosterically links the LBD homodimer interface with the coactivator cleft, thus providing a plausible explanation for distinct PGC-1alpha binding to ERRalpha monomers and homodimers.
About this Structure
3D24 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Communication between the ERR alpha homodimer interface and the PGC-1alpha binding surface vie the helix 8-9 loop., Greschik H, Althage M, Flaig R, Sato Y, Peluso-Iltis C, Chavant V, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D, J Biol Chem. 2008 Apr 25;. PMID:18441008 Page seeded by OCA on Wed Jun 11 10:50:58 2008
Categories: Homo sapiens | Protein complex | Flaig, R. | Greschik, H. | Moras, D. | Rochel, N. | SPINE, Structural Proteomics in Europe. | Sato, Y. | Coactivator | Dna-binding | Ligand binding domain | Metal-binding | Nuclear receptor | Nucleus | Phosphoprotein | Polymorphism | Rna-binding | Spine | Structural genomic | Structural proteomics in europe | Transcription | Transcription regulation | Zinc | Zinc-finger
