Abstract:
:The corticotropin-releasing factor (CRF) ligand family has diverse effects on the CNS, including the modulation of the stress response. The ligands' effects are mediated by binding to CRF G protein-coupled receptors. We have determined the 3D NMR structure of the N-terminal extracellular domain (ECD1) of the mouse CRF receptor 2beta, which is the major ligand recognition domain, and identified its ligand binding site by chemical-shift perturbation experiments. The fold is identified as a short consensus repeat (SCR), a common protein interaction module. Mutagenesis reveals the integrity of the hormone-binding site in the full-length receptor. This study proposes that the ECD1 captures the C-terminal segment of the ligand, whose N terminus then penetrates into the transmembrane region of the receptor to initiate signaling. Key residues of SCR in the ECD1 are conserved in the G protein-coupled receptor subfamily, suggesting the SCR fold in all of the ECD1s of this subfamily.
journal_name
Proc Natl Acad Sci U S Aauthors
Grace CR,Perrin MH,DiGruccio MR,Miller CL,Rivier JE,Vale WW,Riek Rdoi
10.1073/pnas.0404702101keywords:
subject
Has Abstractpub_date
2004-08-31 00:00:00pages
12836-41issue
35eissn
0027-8424issn
1091-6490pii
0404702101journal_volume
101pub_type
杂志文章abstract::Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta. These serine residues of GSK-3 have ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.220413597
更新日期:2000-10-24 00:00:00
abstract::Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.6.1790
更新日期:1985-03-01 00:00:00
abstract::Several 400- to 800-kb murine chromosome domains switch from early to late replication during loss of pluripotency, accompanied by a stable form of gene silencing that is resistant to reprogramming. We found that, whereas enhanced nuclease accessibility correlated with early replication genome-wide, domains that switc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1207185109
更新日期:2012-07-31 00:00:00
abstract::The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends major output signals to the subparaventricular zone (SPZ) and further to the paraventricular nucleus (PVN), the neural mechanism of which is largely unknown. In this study, the intracellular calcium levels were measured continuously in cul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1804300115
更新日期:2018-10-02 00:00:00
abstract::Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited reductions in BFCN size and number and regressive changes in the hippocampal terminal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.181219298
更新日期:2001-08-28 00:00:00
abstract::Proteases constitute the largest enzyme family, yet their biological roles are obscured by our rudimentary understanding of their cellular substrates. There are 12 human caspases that play crucial roles in inflammation and cell differentiation and drive the terminal stages of cell death. Recent N-terminomics technolog...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1524900113
更新日期:2016-04-05 00:00:00
abstract::As global climate continues to warm, melting of glaciers releases a large quantity of mercury (Hg) originally locked in ice into the atmosphere and downstream ecosystems. Here, we show an opposite process that captures atmospheric Hg through glacier-to-vegetation succession. Our study using stable isotope techniques a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906930117
更新日期:2020-01-28 00:00:00
abstract::Extended defects are known to have critical influences in achieving desired material performance. However, the nature of extended defect generation is highly elusive due to the presence of multiple nucleation mechanisms with close energetics. A strategy to design extended defects in a simple and clean way is thus high...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1808812115
更新日期:2018-09-18 00:00:00
abstract::A system is described for assembling infectious bacteriophage phi 6 nucleocapsids in vitro. Procapsids encoded by cDNA copies of genomic segment L in Escherichia coli were used to package and replicate viral RNA segments. The resulting filled particles were shown to be capable of infecting host cell spheroplasts after...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.23.9173
更新日期:1990-12-01 00:00:00
abstract::To investigate how T cells recognize allogeneic class I proteins encoded by the major histocompatibility complex (MHC), we examined the human cytotoxic T lymphocytes (CTL) elicited in a mixed lymphocyte reaction against a lymphoblastoid B-cell line (JY) whose MHC-class I proteins are HLA-A2 and -B7. By panning the res...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.8.2728
更新日期:1988-04-01 00:00:00
abstract::Although sexual selection theory has proved successful in explaining a wide array of male ornaments, the function of ornaments occurring in females is largely unknown. Traditionally, female ornaments have been considered nonfunctional, being merely a genetically correlated response to selection for male ornamentation....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.211439298
更新日期:2001-11-06 00:00:00
abstract::Chemokines play a key role in inflammation. They are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types, including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. Here, we investigated a possible neuroendocrine role of the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0602620103
更新日期:2006-05-23 00:00:00
abstract::The wetting of microstructured surfaces is studied both experimentally and theoretically. Even relatively simple surface topographies such as grooves with rectangular cross section exhibit a large variety of different wetting morphologies as observed by atomic force microscopy. This polymorphism arises from liquid wed...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407721102
更新日期:2005-02-08 00:00:00
abstract::Biochemical and genetic studies have implicated alpha-gustducin as a key component in the transduction of both bitter or sweet taste. Yet, alpha-gustducin-null mice are not completely unresponsive to bitter or sweet compounds. To gain insights into how gustducin mediates responses to bitter and sweet compounds, and to...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.151235798
更新日期:2001-07-17 00:00:00
abstract::We investigate the role of identity and self-image consideration under "pay-what-you-want" pricing. Results from three field experiments show that often, when granted the opportunity to name the price of a product, fewer consumers choose to buy it than when the price is fixed and low. We show that this opt-out behavio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1120893109
更新日期:2012-05-08 00:00:00
abstract::The effects of NusA on the RNA polymerase contacts made by nucleotides at internal positions in the nascent RNA in Escherichia coli transcription complexes were analyzed by using the photocrosslinking nucleotide analog 5-[(4-azidophenacyl) thio]-UMP. It was placed at nucleotides between +6 and +15 in RNA transcribed f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.11.5012
更新日期:1995-05-23 00:00:00
abstract::Ferredoxin was isolated from individual Leucaena glauca trees, and the distribution of amino acids at three of the four sites of sequence heterogeneity was determined. The results indicated that the most probable causes of the observed microheterogeneity are the presence of either nonallelic nuclear genes or differing...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.63.4.1269
更新日期:1969-08-01 00:00:00
abstract::Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1213364110
更新日期:2013-02-12 00:00:00
abstract::Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4(+) T cells. Such in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1302634110
更新日期:2013-07-16 00:00:00
abstract::The prefrontal cortex plays a fundamental role in the working memory functions of the cerebral cortex and is also the site of dysfunction in several neurological and psychiatric disorders, including schizophrenia. Prefrontal neurons are distinguished by their capacity for sustained activity during the time a stimulus ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.011524298
更新日期:2001-01-02 00:00:00
abstract::The cell surface of embryonic peripheral neurons provides a mitogenic stimulus for Schwann cells. We report (i) the solubilization of this mitogenic activity from rat dorsal root ganglion neurons grown in tissue culture and (ii) the solubilization and partial purification of mitogenic activity from neonatal rat brains...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.18.6992
更新日期:1988-09-01 00:00:00
abstract::In virtually every real-life situation humans are confronted with complex and cluttered visual environments that contain a multitude of objects. Because of the limited capacity of the visual system, objects compete for neural representation and cognitive processing resources. Previous work has shown that such attentio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1400559111
更新日期:2014-07-29 00:00:00
abstract::Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.6.1829
更新日期:1976-06-01 00:00:00
abstract::Increased clouds and precipitation normally decrease the diurnal temperature range (DTR) and thus have commonly been offered as explanation for the trend of reduced DTR observed for many land areas over the last several decades. Observations show, however, that the DTR was reduced most in dry regions and especially in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0700290104
更新日期:2007-11-13 00:00:00
abstract::The Mauer mandible, holotype of Homo heidelbergensis, was found in 1907 in fluvial sands deposited by the Neckar River 10 km southeast of Heidelberg, Germany. The fossil is an important key to understanding early human occupation of Europe north of the Alps. Given the associated mammal fauna and the geological context...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1012722107
更新日期:2010-11-16 00:00:00
abstract::Previous studies have shown that the immunosuppressive and carcinogenic polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) impairs Ca(2+)-dependent transmembrane signaling in human and murine lymphocytes. The purpose of the present studies was to analyze potential mechanisms of immunosuppression by ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.13.6105
更新日期:1993-07-01 00:00:00
abstract::Astrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1617330114
更新日期:2017-07-11 00:00:00
abstract::We previously reported that laminar flow activates peroxisome proliferator-activated receptor gamma (PPARgamma) in vascular endothelial cells in a ligand-dependent manner that involves phospholipase A2 and cytochrome P450 epoxygenases. In this study, we investigated whether epoxyeicosatrienoic acids (EETs), the cataly...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0508081102
更新日期:2005-11-15 00:00:00
abstract::After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. Th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.13.5134
更新日期:1990-07-01 00:00:00
abstract::The synthesis of cytoplasmic proteins from quiescent and serum-stimulated Swiss 3T3 cells was compared by two-dimensional polyacrylamide gel electrophoresis. Four new proteins of Mrs 26,000, 28,000, 45,000, and 47,000 designated N26, N28, N45, and N47, which were not detectable in quiescent cells, appeared 60 min afte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.9.5712
更新日期:1981-09-01 00:00:00