Structure and permeation mechanism of a mammalian urea transporter.

Abstract:

:As an adaptation to infrequent access to water, terrestrial mammals produce urine that is hyperosmotic to plasma. To prevent osmotic diuresis by the large quantity of urea generated by protein catabolism, the kidney epithelia contain facilitative urea transporters (UTs) that allow rapid equilibration between the urinary space and the hyperosmotic interstitium. Here we report the first X-ray crystal structure of a mammalian UT, UT-B, at a resolution of 2.36 Å. UT-B is a homotrimer and each protomer contains a urea conduction pore with a narrow selectivity filter. Structural analyses and molecular dynamics simulations showed that the selectivity filter has two urea binding sites separated by an approximately 5.0 kcal/mol energy barrier. Functional studies showed that the rate of urea conduction in UT-B is increased by hypoosmotic stress, and that the site of osmoregulation coincides with the location of the energy barrier.

authors

Levin EJ,Cao Y,Enkavi G,Quick M,Pan Y,Tajkhorshid E,Zhou M

doi

10.1073/pnas.1207362109

subject

Has Abstract

pub_date

2012-07-10 00:00:00

pages

11194-9

issue

28

eissn

0027-8424

issn

1091-6490

pii

1207362109

journal_volume

109

pub_type

杂志文章
  • Palmitoylation influences the function and pharmacology of sodium channels.

    abstract::Palmitoylation is a common lipid modification known to regulate the functional properties of various proteins and is a vital step in the biosynthesis of voltage-activated sodium (Nav) channels. We discovered a mutation in an intracellular loop of rNav1.2a (G1079C), which results in a higher apparent affinity for exter...

    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.1108497108

    authors: Bosmans F,Milescu M,Swartz KJ

    更新日期:2011-12-13 00:00:00

  • Neural mechanisms of social decision-making in the primate amygdala.

    abstract::Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala ...

    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.1514761112

    authors: Chang SW,Fagan NA,Toda K,Utevsky AV,Pearson JM,Platt ML

    更新日期:2015-12-29 00:00:00

  • Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is believed to arise through a multistep model comprised of putative precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). Recent genetically engineered mouse models of PDAC demonstrate a comparable morphologic spectrum of murine PanIN (mPanIN) lesions. The hi...

    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.0810097105

    authors: Habbe N,Shi G,Meguid RA,Fendrich V,Esni F,Chen H,Feldmann G,Stoffers DA,Konieczny SF,Leach SD,Maitra A

    更新日期:2008-12-02 00:00:00

  • ATP-dependent bioluminescence in the firefly squid, Watasenia scintillans.

    abstract::The Japanese firefly squid, Watasenia scintillans, emits intense flashes of light from three tiny luminous organs that are located at the tip of each of a pair of ventral arms. Light is also produced from hundreds of other minute organs that are scattered over the body. The luminescence is due to an ATP-dependent reac...

    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.82.14.4629

    authors: Tsuji FI

    更新日期:1985-07-01 00:00:00

  • Crystallographic properties of the MoFe proteins of nitrogenase from Clostridium pasteurianum and Azotobacter vinelandii.

    abstract::Preliminary x-ray diffraction data from single crystals of the MoFe proteins of nitrogenase from Clostridium pasteurianum and Azotobacter vinelandii have been obtained. Both protein crystals belong to the P2(1) space group. The MoFe protein crystals from C. pasteurianum and A. vinelandii diffract to angles correspondi...

    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.79.2.378

    authors: Weininger MS,Mortenson LE

    更新日期:1982-01-01 00:00:00

  • Signaling in the elicitation process is mediated through the octadecanoid pathway leading to jasmonic acid.

    abstract::Fungal cell walls and fragments thereof (elicitors) induce the formation of low and high molecular weight defense compounds in plant cell suspension cultures. This induced synthesis requires a signal molecule transmitting the message between the elicitor plant cell wall receptor and gene activation. We demonstrate 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.90.16.7490

    authors: Mueller MJ,Brodschelm W,Spannagl E,Zenk MH

    更新日期:1993-08-15 00:00:00

  • Ribonuclease BN: identification and partial characterization of a new tRNA processing enzyme.

    abstract::A new ribonuclease, RNase BN, has been identified and partially purified from a strain of Escherichia coli lacking RNase II and RNase D by using the artificial tRNA precursor tRNA-C-[14C]U as substrate. This enzyme is present in E. coli B but absent from the tRNA processing mutant strain BN which is unable to process ...

    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.80.11.3301

    authors: Asha PK,Blouin RT,Zaniewski R,Deutscher MP

    更新日期:1983-06-01 00:00:00

  • RNA sequences complementary to citrus exocortis viroid in nucleic acid preparations from infected Gynura aurantiaca.

    abstract::Molecular hybridization with (125)I-labeled citrus exocortis viroid RNA has been used to survey nucleic acid preparations from Gynura aurantiaca for viroid complementary molecules. A differential hybridization effect was detected between nucleic acid extracts from healthy and infected tissue in which significant RNase...

    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.75.2.896

    authors: Grill LK,Semancik JS

    更新日期:1978-02-01 00:00:00

  • Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN.

    abstract::It is widely accepted that the heavily glycosylated glycoprotein gp120 on the surface of HIV-1 shields peptide epitopes from recognition by the immune system and may promote infection in vivo by interaction with dendritic cells and transport to tissue rich in CD4(+) T cells such as lymph nodes. A conserved cluster of ...

    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.0712326105

    authors: Wang SK,Liang PH,Astronomo RD,Hsu TL,Hsieh SL,Burton DR,Wong CH

    更新日期:2008-03-11 00:00:00

  • A strategy for the identification of proteins targeted by thioredoxin.

    abstract::Thioredoxins are 12-kDa proteins functional in the regulation of cellular processes throughout the animal, plant, and microbial kingdoms. Growing evidence with seeds suggests that an h-type of thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, reduces disulfide bonds of target proteins and thereby acts as 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.071041998

    authors: Yano H,Wong JH,Lee YM,Cho MJ,Buchanan BB

    更新日期:2001-04-10 00:00:00

  • Convergent evolution of apolipoprotein(a) in primates and hedgehog.

    abstract::Apolipoprotein(a) [apo(a)] is the distinguishing protein component of lipoprotein(a), a major inherited risk factor for atherosclerosis. Human apo(a) is homologous to plasminogen. It contains from 15 to 50 repeated domains closely related to plasminogen kringle four, plus single kringle five-like and inactive protease...

    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.94.22.11992

    authors: Lawn RM,Schwartz K,Patthy L

    更新日期:1997-10-28 00:00:00

  • Formation of an RNA primer for initiation of replication of ColE1 DNA by ribonuclease H.

    abstract::A plasmid that consists of an 812-base-pair segment containing the replication origin of plasmid ColE1 and of a 1240-base-pair segment containing a beta-lactamase gene has been constructed. The plasmid DNA has three principal sites where transcription is initiated in vitro. One is located in the ColE1 segment 555 nucl...

    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.77.5.2450

    authors: Itoh T,Tomizawa J

    更新日期:1980-05-01 00:00:00

  • Electrocatalytically driven omega-hydroxylation of fatty acids using cytochrome P450 4A1.

    abstract::The cyclic enzymatic function of a cytochrome P450, as it catalyzes the oxygen-dependent metabolism of many organic chemicals, requires the delivery of two electrons to the hemeprotein. In general these electrons are transferred from NADPH to the P450 via an FMN- and FAD-containing flavoprotein (NADPH-P450 reductase)....

    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.92.17.7705

    authors: Faulkner KM,Shet MS,Fisher CW,Estabrook RW

    更新日期:1995-08-15 00:00:00

  • Bulk electronic transport impacts on electron transfer at conducting polymer electrode-electrolyte interfaces.

    abstract::Electrochemistry is an old but still flourishing field of research due to the importance of the efficiency and kinetics of electrochemical reactions in industrial processes and (bio-)electrochemical devices. The heterogeneous electron transfer from an electrode to a reactant in the solution has been well studied for m...

    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.1806087115

    authors: Wijeratne K,Ail U,Brooke R,Vagin M,Liu X,Fahlman M,Crispin X

    更新日期:2018-11-20 00:00:00

  • On the trend, detrending, and variability of nonlinear and nonstationary time series.

    abstract::Determining trend and implementing detrending operations are important steps in data analysis. Yet there is no precise definition of "trend" nor any logical algorithm for extracting it. As a result, various ad hoc extrinsic methods have been used to determine trend and to facilitate a detrending operation. In this art...

    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.0701020104

    authors: Wu Z,Huang NE,Long SR,Peng CK

    更新日期:2007-09-18 00:00:00

  • Efficient expression of Escherichia coli galactokinase gene in mammalian cells.

    abstract::The Escherichia coli galactokinase gene (galK) was inserted into a modified early region transcription unit of simian virus 40 (SV40) contained on a bacterial plasmid. Introduction of this pSVK vector into monkey, mouse, and hamster cell lines by transfection resulted in efficient expression of the bacterial galK gene...

    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.79.2.257

    authors: Schümperli D,Howard BH,Rosenberg M

    更新日期:1982-01-01 00:00:00

  • Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK.

    abstract::Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR re...

    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.1604047113

    authors: Ogawa T,Tsubakiyama R,Kanai M,Koyama T,Fujii T,Iefuji H,Soga T,Kume K,Miyakawa T,Hirata D,Mizunuma M

    更新日期:2016-10-18 00:00:00

  • Molecular basis of transabdominal--a sexually dimorphic mutant of the bithorax complex of Drosophila.

    abstract::Transabdominal (Tab) is a dominant gain-of-function mutation that results in islands of sexually dimorphic abdominal cuticle in the dorsal thorax of the adult fly. This phenotype has complete penetrance and constant expressivity, and we show that it results from ectopic expression of ABD-BII, one of two proteins deriv...

    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.90.4.1566

    authors: Celniker SE,Lewis EB

    更新日期:1993-02-15 00:00:00

  • Covalent linkage of ribonuclease S-peptide to microinjected proteins causes their intracellular degradation to be enhanced during serum withdrawal.

    abstract::The amino-terminal 20 amino acids are required for microinjected ribonuclease A (RNase A) to be taken up by lysosomes and degraded at an enhanced rate during serum withdrawal. We used water-soluble carbodiimides to covalently attach the RNase S-peptide (residues 1-20) to [3H]RNase S-protein (residues 21-124) at unspec...

    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.83.16.5830

    authors: Backer JM,Dice JF

    更新日期:1986-08-01 00:00:00

  • Anti-AMP antibody precipitation of multiply adenylylated forms of glutamine synthetase from Escherichia coli: a model relating both concentration and density of antigenic sites with the antibody-antigen interaction.

    abstract::Sheep antibodies directed against an AMP-bovine serum albumin conjugate exhibit highly specific binding toward AMP. These antibodies bind to the AMP moiety of adenylylated glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] from Escherichia coli and to no other antigenic determinant on the prot...

    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.77.12.7410

    authors: Hohman RJ,Rhee SG,Stadtman ER

    更新日期:1980-12-01 00:00:00

  • IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection.

    abstract::Mounting effective T cell responses is critical for eliciting long-lasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector...

    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.0914500107

    authors: Brooks DG,Walsh KB,Elsaesser H,Oldstone MB

    更新日期:2010-02-16 00:00:00

  • A single negative charge within the pore region of a cGMP-gated channel controls rectification, Ca2+ blockage, and ionic selectivity.

    abstract::Ca2+ ions control the cGMP-gated channel of rod photoreceptor cells from the external and internal face. We studied ion selectivity and blockage by Ca2+ of wild-type and mutant channels in a heterologous expression system. External Ca2+ blocks the inward current at micromolar concentrations in a highly voltage-depende...

    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.91.3.1109

    authors: Eismann E,Müller F,Heinemann SH,Kaupp UB

    更新日期:1994-02-01 00:00:00

  • neurogenin2 elicits the genesis of retinal neurons from cultures of nonneural cells.

    abstract::neurogenin2 (ngn2) encodes a basic helix-loop-helix transcription factor and plays an important role in neurogenesis from migratory neural crest cells. Its role in retinal development is poorly understood. We observed that in the developing chick retina, ngn2 was expressed in a subpopulation of proliferating progenito...

    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.261455698

    authors: Yan RT,Ma WX,Wang SZ

    更新日期:2001-12-18 00:00:00

  • Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.

    abstract::Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in s...

    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.0905063106

    authors: Mattes J,Collison A,Plank M,Phipps S,Foster PS

    更新日期:2009-11-03 00:00:00

  • mRNAs for the immobilization antigens of Paramecium.

    abstract::Immobilization antigens of stock 51 of Paramecium tetraurelia were subjected to electrophoresis in NaDodSO(4)/polyacrylamide gels. Type A is estimated to have a molecular size of 300,000 daltons; H is estimated to be 288,000, D to be 280,000, E to be 270,000, B to be 253,000, and C to be 250,000. Poly(A)(+)RNAs have b...

    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.78.11.6776

    authors: Preer JR,Preer LB,Rudman BM

    更新日期:1981-11-01 00:00:00

  • Associative memory Hamiltonians for structure prediction without homology: alpha/beta proteins.

    abstract::We describe a method for predicting the structure of alpha beta class proteins in the absence of information from homologous structures. The method is based on an associative memory model for short to intermediate range in sequence contacts and a contact potential for long range in sequence contacts. The coefficients ...

    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.252753899

    authors: Hardin C,Eastwood MP,Prentiss MC,Luthey-Schulten Z,Wolynes PG

    更新日期:2003-02-18 00:00:00

  • Part mutual information for quantifying direct associations in networks.

    abstract::Quantitatively identifying direct dependencies between variables is an important task in data analysis, in particular for reconstructing various types of networks and causal relations in science and engineering. One of the most widely used criteria is partial correlation, but it can only measure linearly direct associ...

    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.1522586113

    authors: Zhao J,Zhou Y,Zhang X,Chen L

    更新日期:2016-05-03 00:00:00

  • DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.

    abstract::Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insig...

    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.0408170101

    authors: White EJ,Emanuelsson O,Scalzo D,Royce T,Kosak S,Oakeley EJ,Weissman S,Gerstein M,Groudine M,Snyder M,Schübeler D

    更新日期:2004-12-21 00:00:00

  • The proton pumping pathway of bovine heart cytochrome c oxidase.

    abstract::X-ray structures of bovine heart cytochrome c oxidase have suggested that the enzyme, which reduces O(2) in a process coupled with a proton pumping process, contains a proton pumping pathway (H-pathway) composed of a hydrogen bond network and a water channel located in tandem across the enzyme. The hydrogen bond netwo...

    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.0611627104

    authors: Shimokata K,Katayama Y,Murayama H,Suematsu M,Tsukihara T,Muramoto K,Aoyama H,Yoshikawa S,Shimada H

    更新日期:2007-03-06 00:00:00

  • Herpes simplex virus DNA replication: a spacer sequence directs the ATP-dependent formation of a nucleoprotein complex at oriS.

    abstract::The origin-binding protein (OBP) from herpes simplex virus 1 is a member of the SF2 helicase superfamily and is required for the initiation of DNA synthesis from a viral origin of DNA replication (oriS). The high-affinity binding sites for OBP in oriS, boxes I and II, are separated by an A+T-rich spacer. We used the g...

    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.91.11.4629

    authors: Gustafsson CM,Hammarsten O,Falkenberg M,Elias P

    更新日期:1994-05-24 00:00:00