The N-terminal activation function AF-1 domain of ERα interacts directly with the C-terminal AF-2-holding ligand-binding domain to recruit the coactivator proteins.

ABSTRACT: Cryoelectron microscopy (cryo-EM) clarified the quaternary structure of the DNA complex of coactivator-bound estrogen receptor alpha (ERα), revealing the adjacency of the N-terminal domain (NTD) and C-terminal ligand-binding domain (LBD). ERα-NTD and LBD constitute activation function 1 (AF-1) and activation function 2 (AF-2), respectively. These domains are essential for transcription activation. Their spatial proximity was judged to be essential for ERα to recruit the SRC coactivator proteins. In the present study, we first evaluated untethered free ERα-NTD(AF-1) [residues 1-180] and its-truncated desNTD(AF-1)-ERα [residues 181-595] in a luciferase reporter gene assay. ERα-NTD(AF-1) was completely inactive, whereas desNTD(AF-1)-ERα exhibited 66% activity of wild-type ERα. Surprisingly, E

SUBMITTER: Liu X 

PROVIDER: S-EPMC11493271 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature