4PPS

Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with an A-CD ring estrogen derivative

Summary for 4PPS

• Entry DOI: 10.2210/pdb4pps/pdb
• Related: 4PP6 4PPP
• Descriptor: Estrogen receptor, Nuclear receptor coactivator 2, (1S,3aR,5R,7aS)-5-(4-hydroxyphenyl)-7a-methyloctahydro-1H-inden-1-ol, ... (4 entities in total)
• Functional Keywords: nuclear hormone receptor, transcription factor, ligand-binding, nucleus, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Nucleus. Isoform 3: Nucleus. Nucleus: P03372; Nucleus: Q15596
• Total number of polymer chains: 4
• Total formula weight: 59059.63

Authors

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Parent, A.A.,Hughes, T.S.,Pollock, J.A.,Gjyshi, O.,Cavett, V.,Nowak, J.,Garcia-Ordonez, R.D.,Houtman, R.,Griffin, P.R.,Kojetin, D.J.,Katzenellenbogen, J.A.,Conkright, M.D.,Nettles, K.W. (deposition date: 2014-02-27, release date: 2014-05-07, Last modification date: 2023-09-20)

Primary citation

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Parent, A.A.,Hughes, T.S.,Pollock, J.A.,Gjyshi, O.,Cavett, V.,Nowak, J.,Garcia-Ordonez, R.D.,Houtman, R.,Griffin, P.R.,Kojetin, D.J.,Katzenellenbogen, J.A.,Conkright, M.D.,Nettles, K.W.
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.
Elife, 3:e02057-e02057, 2014

PubMed Abstract: Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity.DOI: http://dx.doi.org/10.7554/eLife.02057.001.

PubMed: 24771768
DOI: 10.7554/eLife.02057

Experimental method

X-RAY DIFFRACTION (1.929 Å)