Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor.

ABSTRACT: Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmiss

SUBMITTER: Kohler C 

PROVIDER: S-EPMC7439413 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature