The quaternary architecture of RAR?-RXR? heterodimer facilitates domain-domain signal transmission.

ABSTRACT: Assessing the physical connections and allosteric communications in multi-domain nuclear receptor (NR) polypeptides has remained challenging, with few crystal structures available to show their overall structural organizations. Here we report the quaternary architecture of multi-domain retinoic acid receptor ?-retinoic X receptor ? (RAR?-RXR?) heterodimer bound to DNA, ligands and coactivator peptides, examined through crystallographic, hydrogen-deuterium exchange mass spectrometry, mutagenesis and functional studies. The RAR? ligand-binding domain (LBD) and DNA-binding domain (DBD) are physically connected to foster allosteric signal transmission between them. Direct comparisons among all the multi-domain NRs studied crystallographically to date show significant variations within their quaternary architectures, rather than a common architecture adhering to strict rules. RXR remains flexible and adaptive by maintaining loosely organized domains, while its heterodimerization partners use a surface patch on their LBDs to form domain-domain interactions with DBDs.Nuclear receptors (NR) are multidomain proteins, which makes their crystallization challenging. Here the authors present the crystal structure of the retinoic acid receptor ?-retinoic X receptor ? (RAR?-RXR?) heterodimer bound to DNA, ligands and coactivator peptides, which shows that NR quaternary architectures are variable.

SUBMITTER: Chandra V 

PROVIDER: S-EPMC5636793 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature