3erd
From Proteopedia
(New page: 200px<br /> <applet load="3erd" size="450" color="white" frame="true" align="right" spinBox="true" caption="3erd, resolution 2.03Å" /> '''HUMAN ESTROGEN RECE...) |
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| - | [[Image:3erd.gif|left|200px]]<br /> | + | [[Image:3erd.gif|left|200px]]<br /><applet load="3erd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="3erd" size=" | + | |
caption="3erd, resolution 2.03Å" /> | caption="3erd, resolution 2.03Å" /> | ||
'''HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH DIETHYLSTILBESTROL AND A GLUCOCORTICOID RECEPTOR INTERACTING PROTEIN 1 NR BOX II PEPTIDE'''<br /> | '''HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH DIETHYLSTILBESTROL AND A GLUCOCORTICOID RECEPTOR INTERACTING PROTEIN 1 NR BOX II PEPTIDE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ligand-dependent activation of transcription by nuclear receptors (NRs) is | + | Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived from the NR box II region of the coactivator GRIP1 and the crystal structure of the hER alpha LBD bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the DES-LBD-peptide complex, the peptide binds as a short alpha helix to a hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the interactions of the NR box peptide with the LBD. These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 3ERD 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 CL, DES and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 3ERD 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 <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=DES:'>DES</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2ERD. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ERD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Agard, D | + | [[Category: Agard, D A.]] |
[[Category: Barstad, D.]] | [[Category: Barstad, D.]] | ||
[[Category: Cheng, L.]] | [[Category: Cheng, L.]] | ||
| - | [[Category: Greene, G | + | [[Category: Greene, G L.]] |
| - | [[Category: Kushner, P | + | [[Category: Kushner, P J.]] |
| - | [[Category: Loria, P | + | [[Category: Loria, P M.]] |
| - | [[Category: Shiau, A | + | [[Category: Shiau, A K.]] |
[[Category: ACY]] | [[Category: ACY]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:09:13 2008'' |
Revision as of 17:09, 21 February 2008
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HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH DIETHYLSTILBESTROL AND A GLUCOCORTICOID RECEPTOR INTERACTING PROTEIN 1 NR BOX II PEPTIDE
Contents |
Overview
Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived from the NR box II region of the coactivator GRIP1 and the crystal structure of the hER alpha LBD bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the DES-LBD-peptide complex, the peptide binds as a short alpha helix to a hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the interactions of the NR box peptide with the LBD. These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.
Disease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this Structure
3ERD is a Protein complex structure of sequences from Homo sapiens with , and as ligands. This structure supersedes the now removed PDB entry 2ERD. Full crystallographic information is available from OCA.
Reference
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen., Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL, Cell. 1998 Dec 23;95(7):927-37. PMID:9875847
Page seeded by OCA on Thu Feb 21 19:09:13 2008
Categories: Homo sapiens | Protein complex | Agard, D A. | Barstad, D. | Cheng, L. | Greene, G L. | Kushner, P J. | Loria, P M. | Shiau, A K. | ACY | CL | DES | Agonist | Coactivator | Estrogen | Nuclear receptor | Transcription factor
