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.
journal_name
Celljournal_title
Cellauthors
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 HEdoi
10.1016/s0092-8674(02)00817-6subject
Has Abstractpub_date
2002-07-12 00:00:00pages
93-105issue
1eissn
0092-8674issn
1097-4172pii
S0092867402008176journal_volume
110pub_type
杂志文章相关文献
CELL文献大全abstract：:The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophage...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.12.039
更新日期：2006-03-10 00:00:00
abstract：:To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.04.014
更新日期：2017-05-04 00:00:00
abstract：:Syntaxin 1A plays a central role in neurotransmitter release through multiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-terminal domain is conserved in plasma membr...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81742-0
更新日期：1998-09-18 00:00:00
abstract：:Transcriptional pausing by multisubunit RNA polymerases (RNAPs) is a key mechanism for regulating gene expression in both prokaryotes and eukaryotes and is a prerequisite for transcription termination. Pausing and termination states are thought to arise through a common, elemental pause state that is inhibitory for nu...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2012.12.020
更新日期：2013-01-31 00:00:00
abstract：:Hybrid transducing phages were constructed in vitro that carry the galK gene fused to each of three ribosomal promoters: the promotor for an rRNA operon (rrnE); the promoter for the spec r protein operon and the promotor for the alpha r protein operon. We also constructed hybrid transducing phages that carry the IacZ ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(81)90185-9
更新日期：1981-09-01 00:00:00
abstract：:It was previously demonstrated that the 60,000 dalton (p60) precursor-like polyprotein containing murine p30 was a constituent of the feline leukemia virus pseudotype of Moloney sarcoma virus [m1MSV(FeLV)]. It is now shown that p60 is detected in cells of five mammalian species transformed by m1MSV, indicating that p...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(77)90142-8
更新日期：1977-01-01 00:00:00
abstract：:Neurons in cortical circuits are often coactivated as ensembles, yet it is unclear whether ensembles play a functional role in behavior. Some ensemble neurons have pattern completion properties, triggering the entire ensemble when activated. Using two-photon holographic optogenetics in mouse primary visual cortex, we ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.05.045
更新日期：2019-07-11 00:00:00
abstract：:Advances in genomic technology have produced an explosion of new information about the genetic basis for human disease, fueling extraordinarily high expectations for improved treatments. This perspective will take brief stock of what genetics/genomics have brought to clinical practice to date and what we might expect ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2011.09.013
更新日期：2011-09-30 00:00:00
abstract：:We have identified mutations in Drosophila endophilin to study its function in vivo. Endophilin is required presynaptically at the neuromuscular junction, and absence of Endophilin dramatically impairs endocytosis in vivo. Mutant larvae that lack Endophilin fail to take up FM1-43 dye in synaptic boutons, indicating an...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00688-8
更新日期：2002-04-05 00:00:00
abstract：:New biological tools provide new techniques to probe fundamental biological processes. Here we describe the burgeoning field of proteolysis-targeting chimeras (PROTACs), which are capable of modulating protein concentrations at a post-translational level by co-opting the ubiquitin-proteasome system. We describe the PR...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2019.11.031
更新日期：2020-04-02 00:00:00
abstract：:During HIV infection, the timing of opportunistic infections is not always associated with severity of CD4 T cell depletion, and different opportunistic pathogens reactivate at different CD4 T cell thresholds. Here, we examine how differences in the phenotype and function of pathogen-specific CD4 T cells influence sus...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.09.045
更新日期：2013-10-24 00:00:00
abstract：:Every day we make decisions critical for adaptation and survival. We repeat actions with known consequences. But we also draw on loosely related events to infer and imagine the outcome of entirely novel choices. These inferential decisions are thought to engage a number of brain regions; however, the underlying neuron...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2020.08.035
更新日期：2020-10-01 00:00:00
abstract：:A diverse range of ultimate chemical carcinogens inhibited the transfer of methyl groups from S-adenosylmethionine to hemimethylated DNA in a reaction catalyzed by mouse spleen methyltransferase. The formation of alkali-labile sites in DNA lessened its ability to accept methyl groups in vitro, but the methylation reac...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(83)90514-7
更新日期：1983-01-01 00:00:00
abstract：:Cultured preadipose 3T3 cells are induced or enabled to undergo adipose conversion in the presence of an extract of pituitary gland. Adipogenic activity is found in standard growth hormone preparations derived from different species. Further purification of rat growth hormone by several methods does not remove its adi...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(82)90440-8
更新日期：1982-07-01 00:00:00
abstract：:FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00624-4
更新日期：2002-01-25 00:00:00
abstract：:Alterations of symbiosis between microbiota and intestinal epithelial cells (IEC) are associated with intestinal and systemic pathologies. Interactions between bacterial products (MAMPs) and Toll-like receptors (TLRs) are known to be mandatory for IEC homeostasis, but how TLRs may time homeostatic functions with circa...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.04.020
更新日期：2013-05-09 00:00:00
abstract：:Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/S0092-8674(00)80605-4
更新日期：1999-07-09 00:00:00
abstract：:The looming threat of a new influenza virus pandemic has fueled ambitious efforts to devise more predictive parameters for assessing the risks associated with emergent virus strains. At the same time, a comprehensive understanding of critical factors that can accurately predict the outcome of vaccination is sorely nee...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.03.023
更新日期：2014-04-10 00:00:00
abstract：:Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase o...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2020.03.050
更新日期：2020-04-16 00:00:00
abstract：:beta-glucocerebrosidase, the enzyme defective in Gaucher disease, is targeted to the lysosome independently of the mannose-6-phosphate receptor. Affinity-chromatography experiments revealed that the lysosomal integral membrane protein LIMP-2 is a specific binding partner of beta-glucocerebrosidase. This interaction in...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2007.10.018
更新日期：2007-11-16 00:00:00
abstract：:Bacteria can respond to adverse environmental conditions by drastically reducing or even ceasing metabolic activity. They must then determine that conditions have improved before exiting dormancy, and one indication of such a change is the growth of other bacteria in the local environment. Growing bacteria release mur...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.08.039
更新日期：2008-10-31 00:00:00
abstract：:Yeast heat shock protein 104 (Hsp104), the only known eukaryotic disaggregase, remodels both disordered protein aggregates and cross-β sheet amyloids. To handle this diverse clientele, DeSantis et al. report that Hsp104 hexamers use distinct mechanisms-individual subunits are able to dissolve disordered aggregates, bu...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2012.10.033
更新日期：2012-11-09 00:00:00
abstract：:Throughout a 24-h period, the small intestine (SI) is exposed to diurnally varying food- and microbiome-derived antigenic burdens but maintains a strict immune homeostasis, which when perturbed in genetically susceptible individuals, may lead to Crohn disease. Herein, we demonstrate that dietary content and rhythmicit...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2020.08.027
更新日期：2020-09-17 00:00:00
abstract：:Plasmids expressing partial-length sense or antisense protein 4.1 RNA were microinjected into fertilized Xenopus eggs. Nuclease protection assays reveal that antisense protein 4.1 RNA lead to the specific loss of endogenous protein 4.1 transcripts after midblastula transition, with no effect on the levels of three unr...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(88)90576-4
更新日期：1988-05-20 00:00:00
abstract：:In this issue of Cell, discover gene-specific translational silencing as a novel function of the fused glutamyl- and prolyl-tRNA synthetase (GluProRS). GluProRS is released from a multisynthetase translation complex in response to gamma-interferon and forms a four-protein GAIT complex that silences translation of ceru...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2004.10.001
更新日期：2004-10-15 00:00:00
abstract：:We have produced a series of somatic cell hybrids by fusing pluripotent PCC4aza1 embryonal carcinoma ("teretocarcinoma") cells with thymocytes from young adult mice. When these hybrids form tumors in nu/nu or syngeneic mice, all the tumors contain a range of differentiated tissues, as well as embryonal carcinoma-like ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(76)90051-9
更新日期：1976-09-01 00:00:00
abstract：:We have developed an in vitro system utilizing yeast cell-free extracts to catalyze recombination events between homologous plasmids containing different mutant alleles of the Tet or ARG4 genes. The reaction increased the frequency of Tcr or Arg+ transformants (recombinants) from 2 X 10(-6) to 1-3 X 10(-3). Linearizin...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(83)90113-7
更新日期：1983-12-01 00:00:00
abstract：:Elements controlling tissue-specific expression of the rat albumin gene reside within roughly 150 bp upstream of the transcriptional initiation site. We show here by DNAase I footprinting assays that at least four distinct factors present in extracts derived from cells expressing albumin interact with these sequences....
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(87)90036-5
更新日期：1987-08-14 00:00:00
abstract：:We examine the interaction between polyoma-virus-encoded middle tumor antigen and the cellular src gene product, pp60c-src, using a series of monoclonal antibodies that recognize mammalian pp60c-src. Our results show that infection of mouse cells with transformation-competent strains of polyoma virus results in the st...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90272-1
更新日期：1984-10-01 00:00:00
abstract：:Adult neovascularization relies on the recruitment of circulating cells, but their angiogenic roles and recruitment mechanisms are unclear. We show that the endothelial growth factor VEGF is sufficient for organ homing of circulating mononuclear myeloid cells and is required for their perivascular positioning and rete...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.10.036
更新日期：2006-01-13 00:00:00
