2B23

Human estrogen receptor alpha ligand-binding domain and a glucocorticoid receptor-interacting protein 1 NR box II peptide

Summary for 2B23

• Entry DOI: 10.2210/pdb2b23/pdb
• Related: 2B1V 2B1Z
• Descriptor: Estrogen receptor, Nuclear receptor coactivator 2 (3 entities in total)
• Functional Keywords: estrogen receptor, lbd, grip peptide, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 62215.51

Authors

Rajan, S.S.,Hsieh, R.W.,Sharma, S.K.,Greene, G.L. (deposition date: 2005-09-16, release date: 2006-09-19, Last modification date: 2024-10-16)

Primary citation

Nettles, K.W.,Bruning, J.B.,Gil, G.,Nowak, J.,Sharma, S.K.,Hahm, J.B.,Kulp, K.,Hochberg, R.B.,Zhou, H.,Katzenellenbogen, J.A.,Katzenellenbogen, B.S.,Kim, Y.,Joachmiak, A.,Greene, G.L.
NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses
Nat.Chem.Biol., 4:241-247, 2008

PubMed Abstract: Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.

PubMed: 18344977
DOI: 10.1038/nchembio.76

Experimental method

X-RAY DIFFRACTION (2.1 Å)