9hdf

Glucocorticoid Receptor Ligand Binding Domain in complex with dexamethasone

spinqualitylabelsall models 9hdf, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9hdf is a 32 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.78Å Ligands: CAC, CL, CSO, DEX, EPE, GOL, IMD, PEG, PG4, PGE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NR0B2_HUMAN Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:601665. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. Function NR0B2_HUMAN Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1. Publication Abstract from PubMed The glucocorticoid receptor (GR) is a leading drug target due to its antiinflammatory and immunosuppressive roles. The functional oligomeric conformation of full-length GR (FL-GR), which is key for its biological activity, remains disputed. Here we present a new crystal structure of agonist-bound GR ligand-binding domain (GR-LBD) comprising eight copies of a noncanonical dimer. We verified the biological relevance of this dimer for receptor multimerization in wild-type and selected FL-GR mutants using molecular dynamics and crosslinking-mass spectrometry together with fluorescence microscopy and transcriptomic analysis in living cells. Self-association of this GR-LBD basic dimer in two mutually exclusive assemblies reveals clues for FL-GR multimerization and activity in cells. We propose a model for the structure of multidomain GR based on our new data and suggest a detailed oligomerization pathway. This model reconciles all currently available structural and functional information and provides a more comprehensive understanding of the rare disorder, generalized glucocorticoid resistance. The multimerization pathway of the glucocorticoid receptor.,Alegre-Marti A, Jimenez-Panizo A, Lafuente AL, Johnson TA, Montoya-Novoa I, Peralta-Moreno MN, Montanya-Valluguera P, Ponseti-Pons J, Abella M, Kim S, Diaz M, Vilaseca M, Perez P, Fernandez-Recio J, Rubio-Martinez J, Presman DM, Hager GL, Fuentes-Prior P, Estebanez-Perpina E Nucleic Acids Res. 2025 Oct 14;53(19):gkaf1003. doi: 10.1093/nar/gkaf1003. PMID:41118578 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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