1KV6

X-ray structure of the orphan nuclear receptor ERR3 ligand-binding domain in the constitutively active conformation

Summary for 1KV6

• Entry DOI: 10.2210/pdb1kv6/pdb
• Related: 1ERE 1K4W 3ERD
• Descriptor: ESTROGEN-RELATED RECEPTOR GAMMA, steroid receptor coactivator 1 (3 entities in total)
• Functional Keywords: transcriptionally active conformation in absence of ligand, structural proteomics in europe, spine, structural genomics, gene regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (Probable): P62508
• Total number of polymer chains: 4
• Total formula weight: 55720.89

Authors

Greschik, H.,Wurtz, J.-M.,Sanglier, S.,Bourguet, W.,van Dorsselaer, A.,Moras, D.,Renaud, J.-P.,Structural Proteomics in Europe (SPINE) (deposition date: 2002-01-25, release date: 2003-01-25, Last modification date: 2023-08-16)

Primary citation

Greschik, H.,Wurtz, J.-M.,Sanglier, S.,Bourguet, W.,van Dorsselaer, A.,Moras, D.,Renaud, J.-P.
Structural and Functional Evidence for Ligand-Independent Transcriptional Activation by the Estrogen-Related Receptor 3
Mol.Cell, 9:303-313, 2002

PubMed Abstract: The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor 3 (ERR3) complexed with a steroid receptor coactivator-1 (SRC-1) peptide reveals a transcriptionally active conformation in absence of any ligand. The structure explains why estradiol does not bind ERRs with significant affinity. Docking of the previously reported ERR antagonists, diethylstilbestrol and 4-hydroxytamoxifen, requires structural rearrangements enlarging the ligand binding pocket that can only be accommodated with an antagonist LBD conformation. Mutant receptors in which the ligand binding cavity is filled up by bulkier side chains still interact with SRC-1 in vitro and are transcriptionally active in vivo, but are no longer efficiently inactivated by diethylstilbestrol or 4-hydroxytamoxifen. These results provide structural and functional evidence for ligand-independent transcriptional activation by ERR3.

PubMed: 11864604
DOI: 10.1016/S1097-2765(02)00444-6

Experimental method

X-RAY DIFFRACTION (2.7 Å)