Structural Insights into the Process of GPCR-G Protein Complex Formation.

Abstract:

:The crystal structure of the β2-adrenergic receptor (β2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (β2AR-Gsempty). Unfortunately, the β2AR-Gsempty complex does not provide a clear explanation for G protein coupling specificity. Evidence from several sources suggests the existence of a transient complex between the β2AR and GDP-bound Gs protein (β2AR-GsGDP) that may represent an intermediate on the way to the formation of β2AR-Gsempty and may contribute to coupling specificity. Here we present a structure of the β2AR in complex with the carboxyl terminal 14 amino acids from Gαs along with the structure of the GDP-bound Gs heterotrimer. These structures provide evidence for an alternate interaction between the β2AR and Gs that may represent an intermediate that contributes to Gs coupling specificity.

journal_name

Cell

journal_title

Cell

authors

Liu X,Xu X,Hilger D,Aschauer P,Tiemann JKS,Du Y,Liu H,Hirata K,Sun X,Guixà-González R,Mathiesen JM,Hildebrand PW,Kobilka BK

doi

10.1016/j.cell.2019.04.021

subject

Has Abstract

pub_date

2019-05-16 00:00:00

pages

1243-1251.e12

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(19)30440-4

journal_volume

177

pub_type

杂志文章

相关文献

CELL文献大全
  • Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects.

    abstract::Recent results from diverse organisms point to a self-reinforcing network of interactions among the three best-characterized covalent modifications that mark heterochromatin: histone hypoacetylation, histone H3-Lys9 methylation, and cytosine methylation. These modification systems suggest a mechanistic basis for sprea...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/s0092-8674(02)00644-x

    authors: Richards EJ,Elgin SC

    更新日期:2002-02-22 00:00:00

  • Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.

    abstract::Potassium channels embedded in cell membranes employ gates to regulate K+ current. While a specific constriction in the permeation pathway has historically been implicated in gating, recent reports suggest that the signature ion selectivity filter located in the outer membrane leaflet may be equally important. Inwardl...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2010.05.003

    authors: Clarke OB,Caputo AT,Hill AP,Vandenberg JI,Smith BJ,Gulbis JM

    更新日期:2010-06-11 00:00:00

  • Organization and structure of an E. coli tRNA operon containing seven tRNA genes.

    abstract::The structure and organization on the Escherichia coli chromosome of the gene cluster coding for two methionine tRNAs (tRNAmMet), four glutamine tRNAs (two tRNA1Gln and two tRNA2Gln), and a previously unidentified tRNA (called tRNAx) have been studied by restriction enzyme analysis and DNA sequencing, utilizing a spec...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(81)90288-9

    authors: Nakajima N,Ozeki H,Shimura Y

    更新日期:1981-01-01 00:00:00

  • Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating.

    abstract::An approach to identify backbone conformational changes underlying nicotinic acetylcholine receptor (nAChR) gating was developed. Specific backbone peptide bonds were replaced with an ester, which disrupts backbone hydrogen bonds at the site of mutation. At a conserved proline residue (alphaPro221) in the first transm...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80962-9

    authors: England PM,Zhang Y,Dougherty DA,Lester HA

    更新日期:1999-01-08 00:00:00

  • Crystal structures of T. brucei MRP1/MRP2 guide-RNA binding complex reveal RNA matchmaking mechanism.

    abstract::The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedited mRNAs. To understand the mechanism by which this complex pe...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2006.06.047

    authors: Schumacher MA,Karamooz E,Zíková A,Trantírek L,Lukes J

    更新日期:2006-08-25 00:00:00

  • Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases.

    abstract::The "protective protein" is a glycoprotein that associates with lysosomal beta-galactosidase and neuraminidase and is deficient in the autosomal recessive disorder galactosialidosis. We have isolated the cDNA encoding human "protective protein". The clone recognizes a 2 kb mRNA in normal cells that is not evident in f...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(88)90999-3

    authors: Galjart NJ,Gillemans N,Harris A,van der Horst GT,Verheijen FW,Galjaard H,d'Azzo A

    更新日期:1988-09-09 00:00:00

  • Nerve growth factor is an autocrine survival factor for memory B lymphocytes.

    abstract::Production of nerve growth factor (NGF) was assessed in cultures of human T and B lymphocytes and macrophages. NGF was constitutively produced by B cells only, which also expressed surface p140trk-A and p75NGFR molecules and hence efficiently bound and internalized the cytokine. Neutralization of endogenous NGF caused...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81113-7

    authors: Torcia M,Bracci-Laudiero L,Lucibello M,Nencioni L,Labardi D,Rubartelli A,Cozzolino F,Aloe L,Garaci E

    更新日期:1996-05-03 00:00:00

  • From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II.

    abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.07.033

    authors: Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJ

    更新日期:2013-08-15 00:00:00

  • Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.

    abstract::Complex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplic...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.09.003

    authors: McKeown AN,Bridgham JT,Anderson DW,Murphy MN,Ortlund EA,Thornton JW

    更新日期:2014-09-25 00:00:00

  • Regulation of eukaryotic ribosomal RNA transcription by RNA polymerase modification.

    abstract::Forms of RNA polymerase I prepared from growing or encysted Acanthamoeba are equal in the ability to transcribe poly(dl:dC). Polymerase from cysts, whose rRNA genes are transcriptionally inactive, is unable to utilize the rDNA promoter in vitro, whereas the transcription initiation factor from cysts is fully able to b...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90601-x

    authors: Bateman E,Paule MR

    更新日期:1986-11-07 00:00:00

  • SnapShot: Functions of Tubulin Posttranslational Modifications.

    abstract::Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological proc...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.05.032

    authors: Magiera MM,Singh P,Janke C

    更新日期:2018-05-31 00:00:00

  • A Species-Wide Inventory of NLR Genes and Alleles in Arabidopsis thaliana.

    abstract::Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consi...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2019.07.038

    authors: Van de Weyer AL,Monteiro F,Furzer OJ,Nishimura MT,Cevik V,Witek K,Jones JDG,Dangl JL,Weigel D,Bemm F

    更新日期:2019-08-22 00:00:00

  • GABAAR Modulator for Postpartum Depression.

    abstract::During the postpartum period, the brain's inhibitory GABAA receptors may not recover in time following their reduced numbers during pregnancy. This is likely the cause of postpartum depression prevalent in ∼12% of childbearing women. A new therapy for this condition consists of administering a synthetic neurosteroid d...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.12.016

    authors: Mody I

    更新日期:2019-01-10 00:00:00

  • Characterization of two xenopus somatic 5S DNAs and one minor oocyte-specific 5S DNA.

    abstract::The somatic 5S DNA from X. borealis (Xbs 5S DNA) and X. laevis (Xis 5S DNA) and a minor oocyte-specific 5S DNA from X. laevis (Xit 5S DNA) have been purified, and individual repeating units have been cloned and sequenced. The two somatic 5S DNAs differ from the major oocyte 5S DNAs in having GC-rich spacers, homogeneo...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(80)90241-x

    authors: Peterson RC,Doering JL,Brown DD

    更新日期:1980-05-01 00:00:00

  • Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.

    abstract::The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disrupti...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2020.10.005

    authors: Aid M,Busman-Sahay K,Vidal SJ,Maliga Z,Bondoc S,Starke C,Terry M,Jacobson CA,Wrijil L,Ducat S,Brook OR,Miller AD,Porto M,Pellegrini KL,Pino M,Hoang TN,Chandrashekar A,Patel S,Stephenson K,Bosinger SE,Andersen H,

    更新日期:2020-11-25 00:00:00

  • Alpha-amanitin-resistant D. melanogaster with an altered RNA polymerase II.

    abstract::Following EMS mutagenesis we recovered a mutant of D. melanogaster that grows at concentrations of alpha-amanitin lethal to wild-type. To our knowledge this mutant represents the first example of an amanitin-resistant eucaryotic organism. The amanitin resistance of the mutant (AmaC4) is due to an alteration in its DNA...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(79)90116-8

    authors: Greenleaf AL,Borsett LM,Jiamachello PF,Coulter DE

    更新日期:1979-11-01 00:00:00

  • Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.

    abstract::Epidermal growth factor (EGF) regulates cell proliferation and differentiation by binding to the EGF receptor (EGFR) extracellular region, comprising domains I-IV, with the resultant dimerization of the receptor tyrosine kinase. In this study, the crystal structure of a 2:2 complex of human EGF and the EGFR extracellu...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(02)00963-7

    authors: Ogiso H,Ishitani R,Nureki O,Fukai S,Yamanaka M,Kim JH,Saito K,Sakamoto A,Inoue M,Shirouzu M,Yokoyama S

    更新日期:2002-09-20 00:00:00

  • Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles.

    abstract::Fragile X syndrome results from the expansion of a CGG repeat that is normally interrupted by occasional AGG triplets. Linkage disequilibrium suggests that certain normal haplotypes may contribute unequally to the pool of fragile X chromosomes. Sequence analysis of normal alleles demonstrates haplotype-specific variat...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(94)90134-1

    authors: Kunst CB,Warren ST

    更新日期:1994-06-17 00:00:00

  • Protein kinase C phosphorylates pp60src at a novel site.

    abstract::The transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homolog (pp60c-src) are demonstrated to be phosphorylated at serine 12 in vivo under certain conditions. We propose that protein kinase C is responsible for this modification based on the following evidence. First, the tumor promoters, ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(85)90281-8

    authors: Gould KL,Woodgett JR,Cooper JA,Buss JE,Shalloway D,Hunter T

    更新日期:1985-10-01 00:00:00

  • p53 regulation orchestrates the TGF-beta response.

    abstract::Among its multiple functions, p53 is a critical regulator of TGF-beta responses. Sasai et al. (2008) now identify a new p53 inhibitory protein, XFDL156. During embryonic development, this factor is expressed in the ectoderm germ layer and maintains the pluripotency of ectodermal cells by inhibiting TGF-beta target gen...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2008.05.013

    authors: Piccolo S

    更新日期:2008-05-30 00:00:00

  • Exposing secrets of telomere-telomerase encounters.

    abstract::In order for telomeres to remain functional and stable, they must rendezvous with the enzyme telomerase in a productive manner. In human cells, this interaction is mediated by Cajal bodies as matchmaker, and now Zhong et al. reveal molecular determinants that establish good chemistry between the two partners. ...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2012.07.015

    authors: Noël JF,Wellinger RJ

    更新日期:2012-08-03 00:00:00

  • CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate.

    abstract::We have isolated and characterized a set of overlapping cDNA clones that encode the human centromere autoantigen centromere protein C (CENP-C). The identity of these clones has been established using several criteria. First, they were shown to encode a polypeptide that migrates at the expected position for CENP-C on S...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90538-n

    authors: Saitoh H,Tomkiel J,Cooke CA,Ratrie H 3rd,Maurer M,Rothfield NF,Earnshaw WC

    更新日期:1992-07-10 00:00:00

  • A DNA-dependent protease involved in DNA-protein crosslink repair.

    abstract::Toxic DNA-protein crosslinks (DPCs) arise by ionizing irradiation and UV light, are particularly caused by endogenously produced reactive compounds such as formaldehyde, and also occur during compromised topoisomerase action. Although nucleotide excision repair and homologous recombination contribute to cell survival ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.04.053

    authors: Stingele J,Schwarz MS,Bloemeke N,Wolf PG,Jentsch S

    更新日期:2014-07-17 00:00:00

  • E. coli mutant pleiotropically defective in the export of secreted proteins.

    abstract::A hybrid beta-galactosidase molecule containing a substantial portion of the amino-terminal sequence of the maltose-binding protein is inserted in the cytoplasmic membrane of E. coli; in this location, the protein has very low enzymatic activity. The strain producing it is, therefore, Lac-. Selection for derivatives o...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(81)90184-7

    authors: Oliver DB,Beckwith J

    更新日期:1981-09-01 00:00:00

  • Direct Visualization of Wide Fusion-Fission Pores and Their Highly Varied Dynamics.

    abstract::In this issue of Cell, Shin et al. report the first live-cell imaging of a fusion pore. Directly visualized pores in neuroendocrine cells can be much larger than expected yet not require vesicular full-collapse. These fusion-fission pores have diverse fates arising from opposing dynamin-driven pore constriction and F-...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2018.04.016

    authors: Eyring KW,Tsien RW

    更新日期:2018-05-03 00:00:00

  • YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism.

    abstract::The role of S. cerevisiae YDJ1 protein (YDJ1p) in polypeptide translocation across membranes has been examined. A conditional ydj1 mutant strain (ydj1-151TS) is defective for import of several polypeptides into mitochondria and alpha factor into the endoplasmic reticulum at 37 degrees C. These defects are suppressed b...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(05)80063-7

    authors: Caplan AJ,Cyr DM,Douglas MG

    更新日期:1992-12-24 00:00:00

  • Differential antisense transcription from the Dictyostelium EB4 gene locus: implications on antisense-mediated regulation of mRNA stability.

    abstract::The 2.2 kb mRNA of the Dictyostelium discoideum prespore gene EB4-PSV is constitutively transcribed during growth and development, but the message is only accumulated when cells form aggregates and establish the prespore-prestalk pattern. Disruption of the pattern by mechanical disaggregation results in a rapid loss o...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90130-5

    authors: Hildebrandt M,Nellen W

    更新日期:1992-04-03 00:00:00

  • A male accessory gland peptide that regulates reproductive behavior of female D. melanogaster.

    abstract::The adult male accessory glands of D. melanogaster synthesize and secrete a peptide that represses female sexual receptivity and stimulates oviposition. Normally, this peptide is transferred to females during copulation; however, the peptide shows the same biological activity after purification and subsequent injectio...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(88)90192-4

    authors: Chen PS,Stumm-Zollinger E,Aigaki T,Balmer J,Bienz M,Böhlen P

    更新日期:1988-07-29 00:00:00

  • Smac mimetics and TNFalpha: a dangerous liaison?

    abstract::Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vinc...

    journal_title:Cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.cell.2007.10.042

    authors: Wu H,Tschopp J,Lin SC

    更新日期:2007-11-16 00:00:00

  • Trans-acting nuclear protein responsible for induction of rearranged human immunoglobulin heavy chain gene.

    abstract::A complete human gamma 1 heavy chain gene (HIG1) was transferred into mouse cells by protoplast fusion. The HIG1 gene was strongly expressed in mouse myeloma cells but not in mouse fibroblasts (L cells). Nuclear extracts from myeloma cells were injected into L cell transformants containing one copy of the HIG1 gene; t...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90534-9

    authors: Maeda H,Kitamura D,Kudo A,Araki K,Watanabe T

    更新日期:1986-04-11 00:00:00