Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.

ABSTRACT: Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but for hERα, the detailed structural architecture of the complex is unknown. By utilizing integrated complementary techniques of small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling, here we report an asymmetric L-shaped "boot" structure of the multidomain hERα and identify the specific sites on each domain at the domain interface involved in DBD-LBD interactions. We demonstrate the functional role of the proposed DBD-LBD domain interface

SUBMITTER: Huang W 

PROVIDER: S-EPMC6117352 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature