Abstract:
:AcrAB is a constitutively expressed, major multidrug efflux system of Escherichia coli. We have purified the cytoplasmic membrane component, AcrB, to near homogeneity, and reconstituted the protein into proteoliposomes. In the presence of DeltapH (outside acid), the protein catalyzed the extrusion of fluorescent phospholipids, which were then trapped by protein-free acceptor vesicles. Known substrates of AcrAB, such as bile acids, erythromycin, and cloxacillin, inhibited this activity. Addition of various drugs to AcrB-containing proteoliposomes, in the presence of DeltapH (inside acid) resulted in proton efflux, suggesting that AcrB is a proton antiporter. Interestingly, fluorescent lipid extrusion was accelerated strongly by the periplasmic protein AcrA in the presence of Mg2+, and at pH 5.0 AcrA alone produced a slow mixing of lipids of different vesicles, without causing the mixing of intravesicular material. These results suggest that AcrA brings two membranes together, and under certain conditions may even cause the fusion of at least the outer leaflets of the membranes, contributing to the ability of the AcrAB-TolC system to pump drugs out directly into the medium.
journal_name
Proc Natl Acad Sci U S Aauthors
Zgurskaya HI,Nikaido Hdoi
10.1073/pnas.96.13.7190keywords:
subject
Has Abstractpub_date
1999-06-22 00:00:00pages
7190-5issue
13eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::Climate change is expected to influence the capacities of the land and oceans to act as repositories for anthropogenic CO2 and hence provide a feedback to climate change. A series of experiments with the National Center for Atmospheric Research-Climate System Model 1 coupled carbon-climate model shows that carbon sink...
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.0504949102
更新日期:2005-08-09 00:00:00
abstract::Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) has been implicated in Parkinson's disease (PD) and is present in neurofibrillary tangles or Lewy bodies. However, the molecular basis for UCH-L1s involvement in proteinacious fibril formation is still elusive, especially in regard to the pathogenicity of the I93M muta...
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.1002295107
更新日期:2010-04-13 00:00:00
abstract::We have obtained the electron paramagnetic resonance spectrum of Cu2+ bound in a tetragonal single crystal of hen egg-white lysozyme. A part of this spectrum has been shown to originate from Cu2+ ions bound at the site designated as B by Teichberg et al. [Teichberg, V.I., Sharon, N., Moult, J., Smilansky, A. & Yonath,...
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.77.9.5243
更新日期:1980-09-01 00:00:00
abstract::It is found that the addition of hexamethylphosphoramide to the solution of an alkyne, Et(2)Zn, and (S)-1,1'-bi-2-naphthol in methylene chloride allows the generation of an alkynylzinc at room temperature and shows highly enantioselective additions to aldehydes. The mild condition for the formation of the alkynylzinc ...
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.0307136101
更新日期:2004-04-13 00:00:00
abstract::All decisions, whether they are personal, public, or business-related, are based on the decision maker's beliefs and values. Science can and should help decision makers by shaping their beliefs. Unfortunately, science is not easily accessible to decision makers, and scientists often do not understand decision makers' ...
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.1213532110
更新日期:2013-08-20 00:00:00
abstract::A codon-optimized mouse LINE-1 element, ORFeus, exhibits dramatically higher retrotransposition frequencies compared with its native long interspersed element 1 counterpart. To establish a retrotransposon-mediated mouse model with regulatable and potent mutagenic capabilities, we generated a tetracycline (tet)-regulat...
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.1302504110
更新日期:2013-07-16 00:00:00
abstract::The core enzyme of Escherichia coli RNA polymerase acquires essential promoter recognition and transcription initiation activities by binding one of several sigma subunits. To characterize the proximity between sigma70, the major sigma for transcription of the growth-related genes, and the core enzyme subunits (alpha2...
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.95.11.6021
更新日期:1998-05-26 00:00:00
abstract::A discrepancy of about 20% exists between the molecular weight of the alpha subunit of Torpedo californica electroplax acetylcholine receptor as determined by gel electrophoresis of the mature protein (Mr 40,000 +/- 2000) and by nucleotide sequence analysis of cDNA (Mr approximately equal to 50,000). We demonstrate 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.81.9.2631
更新日期:1984-05-01 00:00:00
abstract::Receptor-binding specificity of HA, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Influenza type B virus almost exclusively infects humans and contributes to the annual "flu" sickness. Here we report the structures of influenza B virus HA in complex ...
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.0708363104
更新日期:2007-10-23 00:00:00
abstract::Tyrosine kinases of the Janus kinase family initiate cellular responses through their association with receptors for alpha-helical cytokines. In addition to a tyrosine kinase domain, these enzymes possess a kinase-like (KL) domain, whose function remains elusive. To investigate the role of the KL domain of Tyk2 in int...
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.160130297
更新日期:2000-08-01 00:00:00
abstract::Despite extensive efforts to understand the monogenic contributions to perturbed glucose homeostasis, the complexity of genetic events that fractionally contribute to the spectrum of this pathology remain poorly understood. Proper maintenance of glucose homeostasis is the central feature of a constellation of comorbid...
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.1519073112
更新日期:2015-11-03 00:00:00
abstract::The absorption spectrum of an activesite specific chromophoric acyl enzyme, sturgeon beta-(2-furyl)-acryloyl-glyceraldehyde-3-phosphate dehydrogenase, is reported. This acyl enzyme undergoes all of the catalyzed reactions characteristic of the intermediate of the physiological acyl enzyme, 3-phospho-D-glyceroyl-glycer...
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.70.7.2077
更新日期:1973-07-01 00:00:00
abstract::The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian se...
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.2136624100
更新日期:2003-12-09 00:00:00
abstract::Little is known about the large ectodomain of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor (HGF/SF). Here, we establish by deletion mutagenesis that the HGF/SF and heparin-binding sites of MET are contained within a large N-terminal domain spanning the alpha-chai...
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.2034936100
更新日期:2003-10-14 00:00:00
abstract::Although most nuclear hormone receptors are ligand-dependent transcriptional activators, certain members of this superfamily, such as thyroid hormone receptor (TR) and retinoic acid receptor (RAR), are involved in transcriptional repression. The silencing function of these receptors has been localized to the ligand bi...
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.92.25.11691
更新日期:1995-12-05 00:00:00
abstract::Under natural viewing conditions the input to the retina is a complex spatiotemporal signal that depends on both the scene and the way the observer moves. It is commonly assumed that the retina processes this input signal efficiently by taking into account the statistics of the natural world. It has recently been argu...
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.1412059112
更新日期:2015-03-10 00:00:00
abstract::As the Conus shell grows by spiraling of the outer lip around the axis, profound internal shell dissolution thins the walls of the protected penultimate whorl from several millimeters to <50mum. Shell material is added to the inside of the spire and the anterior part of the columella. The resulting shell has a uniform...
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.76.7.3406
更新日期:1979-07-01 00:00:00
abstract::The alpha and beta subunits of Na-K-ATPase are up-regulated by hypertonicity in inner-medullary collecting duct cells adapted to survive in hypertonic conditions. We examined the regulation of the gamma subunit by hypertonicity. Although cultured inner-medullary collecting duct cells lacked the gamma subunits, both va...
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.231309198
更新日期:2001-11-06 00:00:00
abstract::The mature optic nerve cannot regenerate when injured, leaving victims of traumatic nerve damage or diseases such as glaucoma with irreversible visual losses. Recent studies have identified ways to stimulate retinal ganglion cells to regenerate axons part-way through the optic nerve, but it remains unknown whether mat...
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.1119449109
更新日期:2012-06-05 00:00:00
abstract::The nucleotide cyclic di-3',5'- adenosine monophosphate (c-di-AMP) was recently identified as an essential and widespread second messenger in bacterial signaling. Among c-di-AMP-producing bacteria, altered nucleotide levels result in several physiological defects and attenuated virulence. Thus, a detailed molecular un...
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.1416485112
更新日期:2015-02-17 00:00:00
abstract::At what range can a mammalian cell sense the presence of another cell and through what medium? To approach these questions, the formation of aggregates of a 3T3 cell variant (3T3x cells) grown on solid substrates was studied. Each of the aggregates consisted of cells that, at the time of their seeding, were single and...
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.0407763102
更新日期:2005-04-05 00:00:00
abstract::Neuropilin-1 (NRP1) is a 130-kDa transmembrane receptor for semaphorins, mediators of neuronal guidance, and for vascular endothelial growth factor 165 (VEGF(165)), an angiogenesis factor. A 2.2-kb truncated NRP1 cDNA was cloned that encodes a 644-aa soluble NRP1 (sNRP1) isoform containing just the a/CUB and b/coagula...
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.040337597
更新日期:2000-03-14 00:00:00
abstract::We report the isolation and functional characterization of cDNAs encoding a Drosophila kainate-selective glutamate receptor. The deduced mature 964-residue protein (DGluR-I) is 108,482 Da and exhibits significant homology to mammalian glutamate receptor subunits. Injection of DGluR-I cRNA into Xenopus oocytes generate...
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.89.21.10484
更新日期:1992-11-01 00:00:00
abstract::Voltage-gated Na(+) channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking...
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.1116449108
更新日期:2011-11-15 00:00:00
abstract::The identification of genes contributing to the adaptation of local populations is of great biological interest. In an attempt to characterize functionally important differences among African and non-African Drosophila melanogaster populations, we surveyed neutral microsatellite variation in an 850-kb genomic sequence...
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.202336899
更新日期:2002-10-01 00:00:00
abstract::We used a sensitive and specific cDNA polymerase chain reaction assay to detect hepatitis C virus (HCV) RNA in serum samples from 128 unselected southern African Blacks with hepatocellular carcinoma (HCC) and found HCV RNA in 26 (20.3%) of these patients. Antibodies to HCV (anti-HCV) were detected in 59 patients (46.1...
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.90.5.1848
更新日期:1993-03-01 00:00:00
abstract::The role of copper/zinc-containing superoxide dismutase (cSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in metabolic defense against O2 toxicity in Drosophila is examined through the properties of a mutant strain carrying a cSOD-null mutation, cSODn108. Homozygotes are viable as larvae, which indicates that ...
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.86.8.2761
更新日期:1989-04-01 00:00:00
abstract::Phagocytosis is a primary defense program orchestrated by monocytes/macrophages. Unregulated phagocytosis can lead to pathological conditions. In the current study we have demonstrated that Wnt5a stimulates phagocytosis through PI3 kinase-Rac1 and lipid-raft-dependent processes. Wnt5a-mediated augmentation in phagocyt...
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.1207789109
更新日期:2012-10-09 00:00:00
abstract::Physiological sensing of O(2) tension (partial O(2) pressure, pO(2)) plays an important role in some mammalian cellular systems, but striated muscle generally is not considered to be among them. Here we describe a molecular mechanism in skeletal muscle that acutely couples changes in pO(2) to altered calcium release t...
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.1109546108
更新日期:2011-09-20 00:00:00
abstract::We describe a strategy to "revive" putatively pathogenic T cells from frozen specimens of human inflammatory target organs. To distinguish pathogenic from irrelevant bystander T cells, we focused on cells that were (i) clonally expanded and (ii) in direct morphological contact with a target cell. Using CDR3 spectratyp...
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.0604247103
更新日期:2006-08-08 00:00:00