2GP7

Estrogen Related Receptor-gamma ligand binding domain

Summary for 2GP7

• Entry DOI: 10.2210/pdb2gp7/pdb
• Descriptor: Estrogen-related receptor gamma, CALCIUM ION (3 entities in total)
• Functional Keywords: estrogen related receptor, err, errg, esrrg, nuclear receptor, steroid receptor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): P62508
• Total number of polymer chains: 4
• Total formula weight: 104377.57

Authors

Wang, L.,Zuercher, W.J.,Consler, T.G.,Lambert, M.H.,Miller, A.B.,Osband-miller, L.A.,McKee, D.D.,Willson, T.M.,Nolte, R.T. (deposition date: 2006-04-17, release date: 2006-09-26, Last modification date: 2023-08-30)

Primary citation

Wang, L.,Zuercher, W.J.,Consler, T.G.,Lambert, M.H.,Miller, A.B.,Orband-Miller, L.A.,McKee, D.D.,Willson, T.M.,Nolte, R.T.
X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation.
J.Biol.Chem., 281:37773-37781, 2006

PubMed Abstract: X-ray crystal structures of the ligand binding domain (LBD) of the estrogen-related receptor-gamma (ERRgamma) were determined that describe this receptor in three distinct states: unliganded, inverse agonist bound, and agonist bound. Two structures were solved for the unliganded state, the ERRgamma LBD alone, and in complex with a coregulator peptide representing a portion of receptor interacting protein 140 (RIP140). No significant differences were seen between these structures that both exhibited the conformation of ERRgamma seen in studies with other coactivators. Two structures were obtained describing the inverse agonist-bound state, the ERRgamma LBD with 4-hydroxytamoxifen (4-OHT), and the ERRgamma LBD with 4-OHT and a peptide representing a portion of the silencing mediator of retinoid and thyroid hormone action protein (SMRT). The 4-OHT structure was similar to other reported inverse agonist bound structures, showing reorientation of phenylalanine 435 and a displacement of the AF-2 helix relative to the unliganded structures with little other rearrangement occurring. No significant changes to the LBD appear to be induced by peptide binding with the addition of the SMRT peptide to the ERRgamma plus 4-OHT complex. The observed agonist-bound state contains the ERRgamma LBD, a ligand (GSK4716), and the RIP140 peptide and reveals an unexpected rearrangement of the phenol-binding residues. Thermal stability studies show that agonist binding leads to global stabilization of the ligand binding domain. In contrast to the conventional mechanism of nuclear receptor ligand activation, activation of ERRgamma by GSK4716 does not appear to involve a major rearrangement or significant stabilization of the C-terminal helix.

PubMed: 16990259
DOI: 10.1074/jbc.M608410200

Experimental method

X-RAY DIFFRACTION (2.45 Å)