2gpp
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Estrogen Related Receptor-gamma ligand binding domain complexed with a RIP140 peptide and synthetic ligand GSK4716
OverviewOverview
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.
About this StructureAbout this Structure
2GPP is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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., Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT, J Biol Chem. 2006 Dec 8;281(49):37773-81. Epub 2006 Sep 21. PMID:16990259
Page seeded by OCA on Wed Jan 23 12:31:29 2008