The conserved sequence NXX[S/T]HX[S/T]QDXXXT of the lactate/pyruvate:H(+) symporter subfamily defines the function of the substrate translocation pathway.

Abstract:

:In Saccharomyces cerevisiae Jen1p is a lactate/proton symporter belonging to the lactate/pyruvate:H(+) symporter subfamily (TC#2.A.1.12.2) of the Major Facilitator Superfamily. We investigated structure-function relationships of Jen1p using a rational mutational analysis based on the identification of conserved amino acid residues. In particular, we studied the conserved sequence (379)NXX[S/T]HX[S/T]QDXXXT(391). Substitution of amino acid residues N379, H383 or D387, even with very similar amino acids, resulted in a dramatic reduction of lactate and pyruvate uptake, but conserved measurable acetate transport. Acetate transport inhibition assays showed that these mutants conserve the ability to bind, but do not transport, lactate and pyruvate. More interestingly, the double mutation H383D/D387H, while behaving as a total loss-of-function allele for lactate and pyruvate uptake, can fully restore the kinetic parameters of Jen1p for acetate transport. Thus, residues N379, H383 or D387 affect both the transport capacity and the specificity of Jen1p. Substitutions of Q386 and T391 resulted in no or moderate changes in Jen1p transport capacities for lactate, pyruvate and acetate. On the other hand, Q386N reduces the binding affinities for all Jen1p substrates, while Q386A increases the affinity specifically for pyruvate. We also tested Jen1p specificity for a range of monocarboxylates. Several of the mutants studied showed altered inhibition constants for these acids. These results and 3D in silico modelling by homology threading suggest that the conserved motif analyzed is part of the substrate translocation pathway in the lactate/pyruvate:H(+) symporter subfamily.

journal_name

Mol Membr Biol

authors

Soares-Silva I,Paiva S,Diallinas G,Casal M

doi

10.1080/09687680701342669

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

464-74

issue

5-6

eissn

0968-7688

issn

1464-5203

pii

779595744

journal_volume

24

pub_type

杂志文章
  • A virtual high-throughput screening approach to the discovery of novel inhibitors of the bacterial leucine transporter, LeuT.

    abstract::Membrane proteins are intrinsically involved in both human and pathogen physiology, and are the target of 60% of all marketed drugs. During the past decade, advances in the studies of membrane proteins using X-ray crystallography, electron microscopy and NMR-based techniques led to the elucidation of over 250 unique m...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687688.2012.710341

    authors: Simmons KJ,Gotfryd K,Billesbølle CB,Loland CJ,Gether U,Fishwick CW,Johnson AP

    更新日期:2013-03-01 00:00:00

  • One membrane protein, two structures and six environments: a comparative molecular dynamics simulation study of the bacterial outer membrane protein PagP.

    abstract::PagP is a bacterial outer membrane protein consisting of an 8 stranded transmembrane beta-barrel and an N-terminal alpha-helix. It is an enzyme which catalyses transfer of a palmitoyl chain from a phospholipid to lipid A. Molecular dynamics simulations have been used to compare the dynamic behaviour in simulations sta...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680902788967

    authors: Cox K,Sansom MS

    更新日期:2009-05-01 00:00:00

  • Intracellular pH regulation in ventral horn neurones cultured from embryonic rat spinal cord.

    abstract::Intracellular pH was measured with the pH-sensitive fluorescent probe BCECF in spinal cord neurones cultured from rat embryos. At an external pH of 7.3, the average steady-state pHi was 7.18 +/- 0.03 (SEM, n = 97) and 7.02 +/- 0.01 (n = 221) in HEPES-buffered and in bicarbonate-buffered medium, respectively. In both e...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680050117129

    authors: Brechenmacher C,Rodeau JL

    更新日期:2000-04-01 00:00:00

  • Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution.

    abstract::Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This rep...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:

    authors: Horton N,Quick MW

    更新日期:2001-01-01 00:00:00

  • Ion channels of glutamate receptors: structural modeling.

    abstract::Ionotropic glutamate receptors belong to the superfamily of P-loop channels as well as K(+), Na(+), and Ca(2+) channels. However, the structural similarity between ion channels of the glutamate receptors and K(+) channels is a matter of discussion. The aim of this study was to analyze differences between the structure...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687860601008806

    authors: Tikhonov DB

    更新日期:2007-03-01 00:00:00

  • Precursor cystatin C in cultured retinal pigment epithelium cells: evidence for processing through the secretory pathway.

    abstract::Evidence was recently reported that the cysteine proteinase inhibitor, cystatin C, is highly expressed by cultured human retinal pigment epithelial (RPE) cells. As a step towards understanding possible functions of this protein associated with the RPE, the localization, targetting and trafficking of cystatin C were in...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680110075101

    authors: Paraoan L,White MR,Spiller DG,Grierson I,Maden BE

    更新日期:2001-07-01 00:00:00

  • Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review).

    abstract::Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse bl...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.3109/09687688.2010.499548

    authors: Huang RB,Mocherla S,Heslinga MJ,Charoenphol P,Eniola-Adefeso O

    更新日期:2010-08-01 00:00:00

  • Rapid determination of the transbilayer distribution of NBD-phospholipids in erythrocyte membranes with dithionite.

    abstract::The assessment of the transverse distribution and mobility of NBD-labelled phospholipid analogues in biological membranes by selective chemical destruction of fluorescent label in the outer monolayer with dithionite has been investigated using resealed erythrocyte ghosts as a model system. The distribution of those an...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689409161028

    authors: Pomorski T,Herrmann A,Zachowski A,Devaux PF,Müller P

    更新日期:1994-01-01 00:00:00

  • TGN38 cycles via the basolateral membrane of polarized Caco-2 cells.

    abstract::TGN38 is a heavily glycosylated, type I integral membrane protein which is predominantly localized to the trans Golgi network (TGN), but which constitutively traffics between the TGN and the cell surface. The trafficking of TGN38 has been extensively studied in non-polarized cells, and a short, tyrosine-based, peptide...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689809074524

    authors: Reaves BJ,Roquemore EP,Luzio JP,Banting G

    更新日期:1998-07-01 00:00:00

  • Identification and biochemical characterization of the SLC9A7 interactome.

    abstract::Organellar and cytosolic pH homeostasis is central to most cellular processes, including vesicular trafficking, post-translational modification/processing of proteins, and receptor-ligand interactions. SLC9A7 (NHE7) was identified as a unique (Na+, K+)/H+ exchanger that dynamically cycles between the trans-Golgi netwo...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680802263046

    authors: Kagami T,Chen S,Memar P,Choi M,Foster LJ,Numata M

    更新日期:2008-08-01 00:00:00

  • The effect of single cerebroside compounds on activation of BKCa channels.

    abstract::We have previously shown that a mixture of cerebrosides obtained from dried tubers of herb Typhonium giganteum Engl. plays a neuroprotective role in the ischemic brain through its effect on activation of BK(Ca) channels. It is very curious to know whether a single pure cerebroside compound could activate the BK(Ca) ch...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687688.2010.538731

    authors: Xu H,Qi J,Wang G,Deng H,Qi Z

    更新日期:2011-02-01 00:00:00

  • Role of glutamate-269 in the lactose permease of Escherichia coli.

    abstract::Glu-269, which is located on the hydrophilic face of putative helix VIII in the lactose permease of Escherichia coli, has been replaced with Asp, Gln or Cys by oligonucleotide-directed, site specific mutagenesis. Cells expressing Asp-269 permease exhibit no lactose accumulation or lactose-induced H+ translocation, but...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689409161024

    authors: Ujwal ML,Sahin-Tóth M,Persson B,Kaback HR

    更新日期:1994-01-01 00:00:00

  • Interactions of the monomeric and dimeric flavones apigenin and amentoflavone with the plasma membrane of L929 cells; a fluorescence study.

    abstract::Flavonoids are ubiquitous polyphenolic compounds, found in vascular plants, which are endowed with a large variety of biological effects. Some of these effects have been assumed to result from interactions with the cell plasma membrane. In order to investigate the nature of these interactions a fluorescence study was ...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/096876899294616

    authors: Lenne-Gouverneur AF,Lobstein A,Haan-Archipoff G,Duportail G,Anton R,Kuhry JG

    更新日期:1999-04-01 00:00:00

  • Cholesterol depletion modulates detergent resistant fraction of human serotonin(1A) receptors.

    abstract::Insolubility of membrane components in non-ionic detergents such as Triton X-100 at low temperature is a widely used biochemical criterion to identify, isolate and characterize membrane domains. In this work, we monitored the detergent insolubility of the serotonin(1A) receptor in CHO cell membranes and its modulation...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687688.2012.688147

    authors: Sahu SK,Saxena R,Chattopadhyay A

    更新日期:2012-11-01 00:00:00

  • Signal recognition particles in chloroplasts, bacteria, yeast and mammals (review).

    abstract::The Signal Recognition Particle (SRP) plays a critical role in the sorting of nascent secretory and membrane proteins. Remarkably, this function has been conserved from bacteria, where SRP delivers proteins to the inner membrane, through to eukaryotes, where SRP is required for targeting of proteins to the endoplasmic...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.1080/09687860400026348

    authors: Pool MR

    更新日期:2005-01-01 00:00:00

  • Time and distance scales of membrane domain organization.

    abstract::Time and distance scales in membranes are discussed in relation to the inference of domain structure from spectroscopic measurements. Each type of spectroscopy has a natural time scale set by the magnitude of the interactions that determine the spectral width. For fluid membranes, the lateral diffusion of the lipid mo...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.3109/09687689509038489

    authors: Bloom M,Thewalt JL

    更新日期:1995-01-01 00:00:00

  • Cross-linking of dimeric CitS and GltS transport proteins.

    abstract::CitS of Klebsiella pneumoniae and GltS of Escherichia coli are Na+-dependent secondary transporters from different families that are believed to share the same fold and quaternary structure. A 10 kDa protein tag (Biotin Acceptor Domain [BAD]) was fused to the N-terminus of both proteins (CitS-BAD1 and GltS-BAD1, respe...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687688.2011.581252

    authors: Krupnik T,Dobrowolski A,Lolkema JS

    更新日期:2011-08-01 00:00:00

  • Functional engineered channels and pores (Review).

    abstract::Significant progress has been made in membrane protein engineering over the last 5 years, based largely on the re-design of existing scaffolds. Engineering techniques that have been employed include direct genetic engineering, both covalent and non-covalent modification, unnatural amino acid mutagenesis and total synt...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.1080/09687680410001716853

    authors: Bayley H,Jayasinghe L

    更新日期:2004-07-01 00:00:00

  • Measurement and characteristics of neurotransmitter receptor surface trafficking (Review).

    abstract::Neurotransmitter receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission during synaptic development and plasticity both at excitatory and inhibitory synapses. Lateral diffusion of surface neurotransmitter receptors has recently emerged as a key pathway to regulate recep...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.1080/09687680801958364

    authors: Groc L,Choquet D

    更新日期:2008-05-01 00:00:00

  • Multiple levels of Notch signal regulation (review).

    abstract::Notch is a vitally important signalling receptor controlling cell fate determination and pattern formation in numerous ways during development of both invertebrate and vertebrate species. An intriguing pathway for the Notch signal has emerged where, after ligand-dependent proteolysis, an intracellular fragment of the ...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.1080/09687680110112929

    authors: Baron M,Aslam H,Flasza M,Fostier M,Higgs JE,Mazaleyrat SL,Wilkin MB

    更新日期:2002-01-01 00:00:00

  • The effect of sterols on structures formed in the gel/subgel phase state of dipalmitoylphosphatidylcholine bilayers.

    abstract::The effect of cholesterol and lanosterol on the formation of structures in the gel/subgel phase of 1,2-dipalmitoylphosphatidylcholine was investigated using freeze-fracture electron microscopy and X-ray diffraction. Mixtures with up to 25 mol% sterol were analysed after annealing for between several days and some mont...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689709048181

    authors: Meyer HW,Semmler K,Quinn PJ

    更新日期:1997-10-01 00:00:00

  • Undecaprenyl diphosphate synthase, a cis-prenyltransferase synthesizing lipid carrier for bacterial cell wall biosynthesis.

    abstract::A group of prenyltransferases produce linear lipids by catalyzing consecutive condensation reactions of farnesyl diphosphate (FPP) with specific numbers of isopentenyl diphosphate (IPP), a common building block of isoprenoid compounds. Depending on the stereochemistry of the double bonds formed during IPP condensation...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.3109/09687688.2012.674162

    authors: Teng KH,Liang PH

    更新日期:2012-11-01 00:00:00

  • Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch.

    abstract::Nedd4 family ubiquitin ligases regulate trafficking and degradation of numerous target substrates in different cellular compartments, including at the plasma membrane, in endosomes, in the secretory pathway and in the nucleus. WWP1 is a Nedd4 family protein closely related to mouse Itch and Drosophila Su(dx), both of ...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687860600665010

    authors: Flasza M,Nguyen Huu NS,Mazaleyrat S,Clémence S,Villemant C,Clarke R,Baron M

    更新日期:2006-05-01 00:00:00

  • Membrane adsorption, folding, insertion and translocation of synthetic trans-membrane peptides.

    abstract::Spontaneous membrane adsorption, folding and insertion of the synthetic WALP16 and KALP16 peptides was studied by computer simulations starting from completely extended conformations. The peptides were simulated using an unmodified all-atom force field in combination with an efficient Monte Carlo sampling algorithm. T...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680802020313

    authors: Ulmschneider MB,Ulmschneider JP

    更新日期:2008-04-01 00:00:00

  • What studies of fusion peptides tell us about viral envelope glycoprotein-mediated membrane fusion (review).

    abstract::This review describes the numerous and innovative methods used to study the structure and function of viral fusion peptides. The systems studied include both intact fusion proteins and synthetic peptides interacting with model membranes. The strategies and methods include dissecting the fusion process into intermediat...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.3109/09687689709048170

    authors: Durell SR,Martin I,Ruysschaert JM,Shai Y,Blumenthal R

    更新日期:1997-07-01 00:00:00

  • Membrane insertion, processing, and topology of cystic fibrosis transmembrane conductance regulator (CFTR) in microsomal membranes.

    abstract::Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated C1(-) channel. Malfunction of CFTR causes cystic fibrosis (CF). CFTR belongs to an ATP-binding cassette (ABC) transporter superfamily which includes P-glycoprotein (Pgp), the molecule that is responsible for multidrug resistance in cancer c...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689609160572

    authors: Chen M,Zhang JT

    更新日期:1996-01-01 00:00:00

  • Membrane binding and transport of N-aminoethyl-1,2-diamino ethane (dien) and N-aminopropyl-1,3-diamino propane (propen) by rat liver mitochondria and their effects on membrane permeability transition.

    abstract::This investigation is aimed at defining the structural requirements for aliphatic polyamines to interact with mitochondrial binding sites, which are relevant for the regulation of the permeability transition and for mitochondrial polyamine uptake. The triamines N-aminoethyl-1,2-diaminoethane (dien) and N-aminopropyl-1...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687680310001654916

    authors: Dalla Via L,Salvi M,Di Noto V,Stefanelli C,Toninello A

    更新日期:2004-03-01 00:00:00

  • In vitro folding of a membrane protein: effect of denaturation and renaturation on substrate binding by the lactose permease of Escherichia coli.

    abstract::Site-directed mutagenesis and site-directed fluorescence spectroscopy demonstrate that Cys148 interacts hydrophobically with the galactosyl moiety of substrates of the lactose permease of Escherichia coli. By taking advantage of the finding that labelling of single-Cys148 permease with the thiol-specific fluorophore 2...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.3109/09687689809027513

    authors: He MM,Kaback HR

    更新日期:1998-01-01 00:00:00

  • Regulation of the calpain-calpastatin system by membranes (review).

    abstract::Calpain, an intracellular calcium-dependent protease, is activated at cell membranes and cleaves cytoskeletal and submembranous proteins. Calpain is inferred to be a calcium-dependent regulator for cytoskeletal reorganization. Calpastatin, an endogenous calpain inhibitor, inhibits not only the proteolytic activity of ...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章,评审

    doi:10.3109/09687689609160599

    authors: Kawasaki H,Kawashima S

    更新日期:1996-10-01 00:00:00

  • Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells.

    abstract::ADP-ribosylation factor related protein 1 (ARFRP1) is a member of the ARF-family of GTPases which operate as molecular switches in the regulation of intracellular protein traffic. Deletion of the mouse Arfrp1 gene leads to embryonic lethality during early gastrulation, suggesting that ARFRP1 is required for cell adhes...

    journal_title:Molecular membrane biology

    pub_type: 杂志文章

    doi:10.1080/09687860600840100

    authors: Zahn C,Hommel A,Lu L,Hong W,Walther DJ,Florian S,Joost HG,Schürmann A

    更新日期:2006-11-01 00:00:00