XL-MS of RORg:RORE:SRC3 Complexes

ABSTRACT: The retinoic acid receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor that both underpins metabolic and immune functions and provides vantage to manipulate those processes pharmacologically. Despite its importance, our understanding of the ligand-dependent activities of RORγ is far from complete and developing a detailed structural model for RORγ pharmacology could provide a path towards the development of safe and efficacious therapeutics targeting the receptor. Herein, we examine the ligand-dependent assembly of recombinant RORγ:coregulator complexes on cognate DNA response elements using structural proteomics and small angle x-ray scattering. These studies reveal that the RORγ DNA binding domain can bind multiple different sequences of DNA, and that coregulatory proteins may be able to ‘sense’ the ligand- and DNA-bound status of RORγ. Overall, the efforts described herein will illuminate important aspects of RORγ activity and drug development that could lead to more efficacious treatments targeting this important receptor.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Timothy Strutzenberg  

LAB HEAD: Patrick Robert Griffin

PROVIDER: PXD025728 | Pride | 2021-11-03

REPOSITORIES: Pride