1kv6
From Proteopedia
(New page: 200px<br /> <applet load="1kv6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kv6, resolution 2.70Å" /> '''X-ray structure of ...) |
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| - | [[Image:1kv6.gif|left|200px]]<br /> | + | [[Image:1kv6.gif|left|200px]]<br /><applet load="1kv6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1kv6" size=" | + | |
caption="1kv6, resolution 2.70Å" /> | caption="1kv6, resolution 2.70Å" /> | ||
'''X-ray structure of the orphan nuclear receptor ERR3 ligand-binding domain in the constitutively active conformation'''<br /> | '''X-ray structure of the orphan nuclear receptor ERR3 ligand-binding domain in the constitutively active conformation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the ligand binding domain (LBD) of the | + | The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor 3 (ERR3) complexed with a steroid receptor coactivator-1 (SRC-1) peptide reveals a transcriptionally active conformation in absence of any ligand. The structure explains why estradiol does not bind ERRs with significant affinity. Docking of the previously reported ERR antagonists, diethylstilbestrol and 4-hydroxytamoxifen, requires structural rearrangements enlarging the ligand binding pocket that can only be accommodated with an antagonist LBD conformation. Mutant receptors in which the ligand binding cavity is filled up by bulkier side chains still interact with SRC-1 in vitro and are transcriptionally active in vivo, but are no longer efficiently inactivated by diethylstilbestrol or 4-hydroxytamoxifen. These results provide structural and functional evidence for ligand-independent transcriptional activation by ERR3. |
==About this Structure== | ==About this Structure== | ||
| - | 1KV6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1KV6 is a [http://en.wikipedia.org/wiki/Protein_complex 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=1KV6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bourguet, W.]] | [[Category: Bourguet, W.]] | ||
| - | [[Category: Dorsselaer, A | + | [[Category: Dorsselaer, A van.]] |
[[Category: Greschik, H.]] | [[Category: Greschik, H.]] | ||
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
| - | [[Category: Renaud, J | + | [[Category: Renaud, J P.]] |
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: Sanglier, S.]] | [[Category: Sanglier, S.]] | ||
| - | [[Category: Wurtz, J | + | [[Category: Wurtz, J M.]] |
[[Category: spine]] | [[Category: spine]] | ||
[[Category: structural genomics]] | [[Category: structural genomics]] | ||
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[[Category: transcriptionally active conformation in absence of ligand]] | [[Category: transcriptionally active conformation in absence of ligand]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:38:14 2008'' |
Revision as of 11:38, 21 February 2008
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X-ray structure of the orphan nuclear receptor ERR3 ligand-binding domain in the constitutively active conformation
Overview
The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor 3 (ERR3) complexed with a steroid receptor coactivator-1 (SRC-1) peptide reveals a transcriptionally active conformation in absence of any ligand. The structure explains why estradiol does not bind ERRs with significant affinity. Docking of the previously reported ERR antagonists, diethylstilbestrol and 4-hydroxytamoxifen, requires structural rearrangements enlarging the ligand binding pocket that can only be accommodated with an antagonist LBD conformation. Mutant receptors in which the ligand binding cavity is filled up by bulkier side chains still interact with SRC-1 in vitro and are transcriptionally active in vivo, but are no longer efficiently inactivated by diethylstilbestrol or 4-hydroxytamoxifen. These results provide structural and functional evidence for ligand-independent transcriptional activation by ERR3.
About this Structure
1KV6 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3., Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP, Mol Cell. 2002 Feb;9(2):303-13. PMID:11864604
Page seeded by OCA on Thu Feb 21 13:38:14 2008
Categories: Homo sapiens | Protein complex | Bourguet, W. | Dorsselaer, A van. | Greschik, H. | Moras, D. | Renaud, J P. | SPINE, Structural Proteomics in Europe. | Sanglier, S. | Wurtz, J M. | Spine | Structural genomics | Structural proteomics in europe | Transcriptionally active conformation in absence of ligand
