Molecular determinants of the estrogen receptor-coactivator interface.

ABSTRACT: Transcriptional activation by the estrogen receptor is mediated through its interaction with coactivator proteins upon ligand binding. By systematic mutagenesis, we have identified a group of conserved hydrophobic residues in the ligand binding domain that are required for binding the p160 family of coactivators. Together with helix 12 and lysine 366 at the C-terminal end of helix 3, they form a hydrophobic groove that accommodates an LXXLL motif, which is essential for mediating coactivator binding to the receptor. Furthermore, we demonstrated that the high-affinity binding of motif 2, conserved in the p160 family, is due to the presence of three basic residues N terminal to the core LXXLL motif. The recruitment of p160 coactivators to the estrogen receptor is therefore likely to depend n

SUBMITTER: Mak HY 

PROVIDER: S-EPMC84247 | biostudies-literature | 1999 May

REPOSITORIES: biostudies-literature