1m2z
Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif
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OverviewOverview
Transcriptional regulation by the glucocorticoid receptor (GR) is mediated, by hormone binding, receptor dimerization, and coactivator recruitment., Here, we report the crystal structure of the human GR ligand binding, domain (LBD) bound to dexamethasone and a coactivator motif derived from, the transcriptional intermediary factor 2. Despite structural similarity, to other steroid receptors, the GR LBD adopts a surprising dimer, configuration involving formation of an intermolecular beta sheet., Functional studies demonstrate that the novel dimer interface is important, for GR-mediated activation. The structure also reveals an additional, charge clamp that determines the binding selectivity of a coactivator and, a distinct ligand binding pocket that explains its selectivity for, endogenous steroid hormones. These results establish a framework for, understanding the roles of protein-hormone and protein-protein, interactions in GR signaling pathways.
DiseaseDisease
Known diseases associated with this structure: Cortisol resistance OMIM:[138040]
About this StructureAbout this Structure
1M2Z is a Protein complex structure of sequences from Homo sapiens with BOG and DEX as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition., Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE, Cell. 2002 Jul 12;110(1):93-105. PMID:12151000
Page seeded by OCA on Mon Nov 12 18:06:31 2007