The quaternary architecture of RARβ-RXRα 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 β-retinoic X receptor α (RARβ-RXRα) heterodimer bound to DNA, ligands and coactivator peptides, examined through crystallographic, hydrogen-deuterium exchange mass spectrometry, mutagenesis and functional studies. The RARβ 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 β-retinoic X receptor α (RARβ-RXRα) heterodimer bound to DNA, ligands and coactivator peptides, which shows that NR quaternary architectures are variable.

journal_name

Nat Commun

journal_title

Nature communications

authors

Chandra V,Wu D,Li S,Potluri N,Kim Y,Rastinejad F

doi

10.1038/s41467-017-00981-y

subject

Has Abstract

pub_date

2017-10-11 00:00:00

pages

868

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00981-y

journal_volume

8

pub_type

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