LB-FP-2 Structure of a DNA-Bound Estrogen Receptor and Coactivator Complex

Program: Late-Breaking Abstracts
Session: SAT-LB-Late-Breaking Poster Session 1
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-LB-03
Ping Yi*1, Zhao Wang2, Qin Feng1, Charles Edward Foulds1, Rainer B Lanz1, Grigore D. Pintilie2, Steven J. Ludtke2, Michael F. Schmid2, Wah Chiu2 and Bert W O'Malley1
1Baylor College of Medicine, Houston, TX, 2Baylor College of Medicine
Estrogen receptor (ER) is a transcription factor critical for development, reproduction, metabolism and cancer. ER function hinges on its ability to recruit primary and secondary coactivators. Portions of ER bound to small peptides of coactivator proteins have been studied structurally, but it is unclear how intact ER and coactivators are assembled into a transcriptionally active complex on DNA. Here we use cryo-EM to determine the quaternary structure of an active complex of DNA-bound ER alpha, steroid receptor coactivator 3 (SRC-3) and a secondary coactivator (p300). Combined with our cryo-EM maps of p300 and other structural information, we identify the spatial relationships in the complex. Each of the two ligand-occupied ER alpha monomers independently recruits one SRC-3 molecule via one of its transactivation function domains; the two SRC-3s in turn bind one molecule of p300 through multiple contacts. The arrangement of these components can explain how p300 is accessible to nearby histones without steric hindrance from the other proteins in the complex. Our structure resolves the stoichiometry of this multi-component assembly of a transcriptionally active nuclear receptor complex.

Nothing to Disclose: PY, ZW, QF, CEF, RBL, GDP, SJL, MFS, WC, BWO

*Please take note of The Endocrine Society's News Embargo Policy at