1m2z: Difference between revisions
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|PDB= 1m2z |SIZE=350|CAPTION= <scene name='initialview01'>1m2z</scene>, resolution 2.50Å | |PDB= 1m2z |SIZE=350|CAPTION= <scene name='initialview01'>1m2z</scene>, resolution 2.50Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene> | |LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2z OCA], [http://www.ebi.ac.uk/pdbsum/1m2z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m2z RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Transcriptional regulation by the glucocorticoid receptor (GR) is mediated by hormone binding, receptor dimerization, and coactivator recruitment. Here, we report the crystal structure of the human GR ligand binding domain (LBD) bound to dexamethasone and a coactivator motif derived from the transcriptional intermediary factor 2. Despite structural similarity to other steroid receptors, the GR LBD adopts a surprising dimer configuration involving formation of an intermolecular beta sheet. Functional studies demonstrate that the novel dimer interface is important for GR-mediated activation. The structure also reveals an additional charge clamp that determines the binding selectivity of a coactivator and a distinct ligand binding pocket that explains its selectivity for endogenous steroid hormones. These results establish a framework for understanding the roles of protein-hormone and protein-protein interactions in GR signaling pathways. | Transcriptional regulation by the glucocorticoid receptor (GR) is mediated by hormone binding, receptor dimerization, and coactivator recruitment. Here, we report the crystal structure of the human GR ligand binding domain (LBD) bound to dexamethasone and a coactivator motif derived from the transcriptional intermediary factor 2. Despite structural similarity to other steroid receptors, the GR LBD adopts a surprising dimer configuration involving formation of an intermolecular beta sheet. Functional studies demonstrate that the novel dimer interface is important for GR-mediated activation. The structure also reveals an additional charge clamp that determines the binding selectivity of a coactivator and a distinct ligand binding pocket that explains its selectivity for endogenous steroid hormones. These results establish a framework for understanding the roles of protein-hormone and protein-protein interactions in GR signaling pathways. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Willson, T M.]] | [[Category: Willson, T M.]] | ||
[[Category: Xu, H E.]] | [[Category: Xu, H E.]] | ||
[[Category: charge clamp]] | [[Category: charge clamp]] | ||
[[Category: coactivator]] | [[Category: coactivator]] | ||
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[[Category: tif2]] | [[Category: tif2]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:10:35 2008'' | ||
Revision as of 22:10, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif
OverviewOverview
Transcriptional regulation by the glucocorticoid receptor (GR) is mediated by hormone binding, receptor dimerization, and coactivator recruitment. Here, we report the crystal structure of the human GR ligand binding domain (LBD) bound to dexamethasone and a coactivator motif derived from the transcriptional intermediary factor 2. Despite structural similarity to other steroid receptors, the GR LBD adopts a surprising dimer configuration involving formation of an intermolecular beta sheet. Functional studies demonstrate that the novel dimer interface is important for GR-mediated activation. The structure also reveals an additional charge clamp that determines the binding selectivity of a coactivator and a distinct ligand binding pocket that explains its selectivity for endogenous steroid hormones. These results establish a framework for understanding the roles of protein-hormone and protein-protein interactions in GR signaling pathways.
About this StructureAbout this Structure
1M2Z is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition., Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE, Cell. 2002 Jul 12;110(1):93-105. PMID:12151000
Page seeded by OCA on Sun Mar 30 22:10:35 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Protein complex
- Apolito, C J.
- Bledsoe, R B.
- Consler, T G.
- Delves, C J.
- Lambert, M H.
- Mckee, D D.
- Montana, V G.
- Moore, J T.
- Parks, D J.
- Pearce, K H.
- Stanley, T B.
- Stewart, E L.
- Willson, T M.
- Xu, H E.
- Charge clamp
- Coactivator
- Dexamethasone
- Dimer interface
- Glucocorticoid receptor
- Hormone binding pocket
- Tif2