3CBM

SET7/9-ER-AdoMet complex

Summary for 3CBM

• Entry DOI: 10.2210/pdb3cbm/pdb
• Related: 3CBO 3CBP
• Descriptor: Histone-lysine N-methyltransferase SETD7, Estrogen receptor, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: estrogen receptor, protein lysine methylation, activator, chromatin regulator, chromosomal protein, methyltransferase, nucleus, s-adenosyl-l-methionine, transcription, transcription regulation, transferase, alternative splicing, dna-binding, lipid-binding, metal-binding, phosphoprotein, polymorphism, steroid-binding, zinc, zinc-finger, transferase-transferase receptor complex, transferase/transferase receptor
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q8WTS6
• Total number of polymer chains: 2
• Total formula weight: 30344.01

Authors

Cheng, X.,Jia, D. (deposition date: 2008-02-22, release date: 2008-05-13, Last modification date: 2023-08-30)

Primary citation

Subramanian, K.,Jia, D.,Kapoor-Vazirani, P.,Powell, D.R.,Collins, R.E.,Sharma, D.,Peng, J.,Cheng, X.,Vertino, P.M.
Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase.
Mol.Cell, 30:336-347, 2008

PubMed Abstract: Estrogen receptor alpha (ER) is a ligand-dependent transcription factor. Upon binding estrogen, ER recruits coactivator complexes with histone acetyltransferase or methyltransferase activities to activate downstream target genes. In addition to histones, coactivators can modify ER itself and other proteins in the transactivation complex. Here, we show that ER is directly methylated at lysine 302 (K302) by the SET7 methyltransferase. SET7-mediated methylation stabilizes ER and is necessary for the efficient recruitment of ER to its target genes and for their transactivation. The SET7-ER complex structure reveals the molecular basis for ER peptide recognition and predicts that modifications or mutations of nearby residues would affect K302 methylation. Indeed, a breast cancer-associated mutation at K303 (K303R) alters methylation at K302 in vitro and in vivo. These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generate "ER modification cassettes" that yield distinct patterns for signaling downstream events.

PubMed: 18471979
DOI: 10.1016/j.molcel.2008.03.022

Experimental method

X-RAY DIFFRACTION (1.69 Å)