1M2Z
Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif
Summary for 1M2Z
| Entry DOI | 10.2210/pdb1m2z/pdb |
| Descriptor | glucocorticoid receptor, nuclear receptor coactivator 2, octyl beta-D-glucopyranoside, ... (5 entities in total) |
| Functional Keywords | glucocorticoid receptor, dexamethasone, tif2, dimer interface, hormone binding pocket, charge clamp, coactivator, hormone-hormone activator complex, hormone/hormone activator |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 66183.12 |
| Authors | Bledsoe, R.B.,Montana, V.G.,Stanley, T.B.,Delves, C.J.,Apolito, C.J.,Mckee, D.D.,Consler, T.G.,Parks, D.J.,Stewart, E.L.,Willson, T.M.,Lambert, M.H.,Moore, J.T.,Pearce, K.H.,Xu, H.E. (deposition date: 2002-06-26, release date: 2003-07-15, Last modification date: 2024-04-03) |
| Primary citation | Bledsoe, R.B.,Montana, V.G.,Stanley, T.B.,Delves, C.J.,Apolito, C.J.,Mckee, D.D.,Consler, T.G.,Parks, D.J.,Stewart, E.L.,Willson, T.M.,Lambert, M.H.,Moore, J.T.,Pearce, K.H.,Xu, H.E. Crystal Structure of the Glucocorticoid Receptor Ligand Binding Domain Reveals a Novel Mode of Receptor Dimerization and Coactivator Recognition Cell(Cambridge,Mass.), 110:93-105, 2002 Cited by PubMed Abstract: 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. PubMed: 12151000DOI: 10.1016/S0092-8674(02)00817-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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