PDBsum entry: 2a65

Transport protein

PDB-id

2a65


	Asymmetric unit

Contents

Description

Header details

Protein chain

Ligands

BOG ×5

LEU

Metal ions

_NA ×2

_CL

Waters ×210

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation

		Biological unit, dimer (as deduced by PQS)

PDB id:

2a65

Name:

Transport protein

Title:

Crystal structure of leutaa, a bacterial homolog of na+/cl-- dependent neurotransmitter transporters

Structure:

Na(+):neurotransmitter symporter (snf family). Chain: a. Synonym: leutaa. Engineered: yes

Source:

Aquifex aeolicus vf5. Organism_taxid: 224324. Strain: vf5. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biological unit:

Dimer (from PQS)

UniProt:

O67854 (O67854_AQUAE)

Seq:

Struc:

Seq:

513 a.a.

Struc:

509 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

1.65Å

R-factor:

0.199

R-free:

0.217

Authors:

A.Yamashita,S.K.Singh,T.Kawate,Y.Jin,E.Gouaux

Key ref:

A.Yamashita et al. (2005). Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters.. Nature, 437, 215-223. [PubMed id: 16041361] [DOI: 10.1038/nature03978]

Date:

01-Jul-05

Release date:

02-Aug-05

Quick_links

RCSB

PDBe

SRS

MMDB

JenaLib

OCA

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

OPM

PQS

ProSAT

Whatcheck

EDS

Procheck

Clefts

Surface

Key reference

DOI no: 10.1038/nature03978 Nature 437:215-223 (2005)

PubMed id: 16041361

Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters.

A.Yamashita, S.K.Singh, T.Kawate, Y.Jin, E.Gouaux.

ABSTRACT

Na+/Cl--dependent transporters terminate synaptic transmission by using electrochemical gradients to drive the uptake of neurotransmitters, including the biogenic amines, from the synapse to the cytoplasm of neurons and glia. These transporters are the targets of therapeutic and illicit compounds, and their dysfunction has been implicated in multiple diseases of the nervous system. Here we present the crystal structure of a bacterial homologue of these transporters from Aquifex aeolicus, in complex with its substrate, leucine, and two sodium ions. The protein core consists of the first ten of twelve transmembrane segments, with segments 1-5 related to 6-10 by a pseudo-two-fold axis in the membrane plane. Leucine and the sodium ions are bound within the protein core, halfway across the membrane bilayer, in an occluded site devoid of water. The leucine and ion binding sites are defined by partially unwound transmembrane helices, with main-chain atoms and helix dipoles having key roles in substrate and ion binding. The structure reveals the architecture of this important class of transporter, illuminates the determinants of substrate binding and ion selectivity, and defines the external and internal gates.

Selected figure(s)

Figure 5.
Figure 5: Extracellular and cytoplasmic gates. a, Slice through the surface of LeuT[Aa], viewed parallel to the membrane, showing the extracellular cavity. Connolly surface of LeuT[Aa] is shown in beige. l-Leucine, Tyr 108, Phe 253 and the two charged pairs (Arg 30 -Asp 404 and Arg 5 -Asp 369) are depicted as stick models in yellow for leucine, purple for aromatic residues, blue for arginines and red for aspartates. b, c, Key interacting residues at the extracellular (b) and at the cytoplasmic (c) gate. Figure 6.
Figure 6: Speculative transport mechanism. Schematic drawing of a possible conformational change upon substrate/sodium ion transport. The left panel shows the outward-facing state. TM1a and TM6b assume the closed arrangement, whereas TM1b and TM6a adopt the open one. The middle panel shows the substrate-occluded state, which corresponds to the current crystal structure. TM1a and TM6b assume the closed arrangement, whereas TM1b and TM6a adopt a partially open one with some residues blocking the permeation pathway. The right panel shows the inward-facing state. TM1b and TM6a assume the closed arrangement, whereas TM1a and TM6b adopt the closed one, to open the pathway to the cytoplasm.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2005, 437, 215-223) copyright 2005.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

19201752 A.Ben-Yona, and B.I.Kanner (2009).
Transmembrane domain 8 of the {gamma}-aminobutyric acid transporter GAT-1 lines a cytoplasmic accessibility pathway into its binding pocket.

J Biol Chem, 284, 9727-9732.

19122974 A.Díez-Sampedro (2009).
Involvement of Amino Acid 36 in TM1 in Voltage Sensitivity in Mouse Na(+)/Glucose Cotransporter SGLT1.

J Membr Biol, 227, 57-66.

19363027 A.K.Meinild, D.D.Loo, S.Skovstrup, U.Gether, and N.Macaulay (2009).
Elucidating Conformational Changes in the {gamma}-Aminobutyric Acid Transporter-1.

J Biol Chem, 284, 16226-16235.

18581270 A.W.Fjorback, H.K.Müller, and O.Wiborg (2009).
Membrane Glycoprotein M6B Interacts with the Human Serotonin Transporter.

J Mol Neurosci, 37, 191-200.

19238460 A.W.Ravna, I.Sylte, and S.G.Dahl (2009).
Structure and localisation of drug binding sites on neurotransmitter transporters.

J Mol Model, 15, 1155-1164.

19419962 C.A.Bippes, A.Zeltina, F.Casagrande, M.Ratera, M.Palacin, D.J.Muller, and D.Fotiadis (2009).
Substrate binding tunes conformational flexibility and kinetic stability of an amino Acid antiporter.

J Biol Chem, 284, 18651-18663.

18977735 E.Gouaux (2009).
Review. The molecular logic of sodium-coupled neurotransmitter transporters.

Philos Trans R Soc Lond B Biol Sci, 364, 149-154.

19219012 E.Schleiff, and R.Tampé (2009).
Membrane proteins take center stage in Frankfurt.

Nat Chem Biol, 5, 135-139.

19458948 F.Orsini, M.Santacroce, P.Arosio, M.Castagna, C.Lenardi, G.Poletti, and F.V.Sacchi (2009).
Intermittent contact mode AFM investigation of native plasma membrane of Xenopus laevis oocyte.

Eur Biophys J, 38, 903-910.

19060912 G.Van Zeebroeck, B.M.Bonini, M.Versele, and J.M.Thevelein (2009).
Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor.

Nat Chem Biol, 5, 45-52.

19458710 H.Krishnamurthy, C.L.Piscitelli, and E.Gouaux (2009).
Unlocking the molecular secrets of sodium-coupled transporters.

Nature, 459, 347-355.

19656393 J.A.Steiner, A.M.Carneiro, J.Wright, H.J.Matthies, H.C.Prasad, C.K.Nicki, W.R.Dostmann, C.C.Buchanan, J.D.Corbin, S.H.Francis, and R.D.Blakely (2009).
cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake.

Mol Brain, 2, 26.

19557250 J.Andersen, A.S.Kristensen, B.Bang-Andersen, and K.Strømgaard (2009).
Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters.

Chem Commun (Camb), 0, 3677-3692.

19213730 J.Andersen, O.Taboureau, K.B.Hansen, L.Olsen, J.Egebjerg, K.Strømgaard, and A.S.Kristensen (2009).
Location of the antidepressant binding site in the serotonin transporter: IMPORTANCE OF SER-438 IN RECOGNITION OF CITALOPRAM AND TRICYCLIC ANTIDEPRESSANTS.

J Biol Chem, 284, 10276-10284.

19651853 J.M.Thevelein, and K.Voordeckers (2009).
Functioning and evolutionary significance of nutrient transceptors.

Mol Biol Evol, 26, 2407-2414.

19147495 K.A.Zaia, and R.J.Reimer (2009).
Synaptic Vesicle Protein NTT4/XT1 (SLC6A17) Catalyzes Na+-coupled Neutral Amino Acid Transport.

J Biol Chem, 284, 8439-8448.

18704946 K.W.Kaufmann, E.S.Dawson, L.K.Henry, J.R.Field, R.D.Blakely, and J.Meiler (2009).
Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies.

Proteins, 74, 630-642.

19478460 M.A.Kurian, J.Zhen, S.Y.Cheng, Y.Li, S.R.Mordekar, P.Jardine, N.V.Morgan, E.Meyer, L.Tee, S.Pasha, E.Wassmer, S.J.Heales, P.Gissen, M.E.Reith, and E.R.Maher (2009).
Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia.

J Clin Invest, 119, 1595-1603.

18792946 M.Alaerts, S.Ceulemans, D.Forero, L.N.Moens, S.De Zutter, L.Heyrman, A.S.Lenaerts, K.F.Norrback, D.Goossens, P.De Rijk, L.G.Nilsson, R.Adolfsson, and J.Del-Favero (2009).
Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population.

Am J Med Genet B Neuropsychiatr Genet, 150, 585-592.

19389142 M.Castagna, E.Bossi, and V.F.Sacchi (2009).
Molecular physiology of the insect K-activated amino acid transporter 1 (KAAT1) and cation-anion activated amino acid transporter/channel 1 (CAATCH1) in the light of the structure of the homologous protein LeuT.

Insect Mol Biol, 18, 265-279.

19621945 M.Czachorowski, S.Lam-Yuk-Tseung, M.Cellier, and P.Gros (2009).
Transmembrane topology of the mammalian Slc11a2 iron transporter.

Biochemistry, 48, 8422-8434.

19380585 M.D.Slugoski, A.M.Ng, S.Y.Yao, C.C.Lin, R.Mulinta, C.E.Cass, S.A.Baldwin, and J.D.Young (2009).
Substituted Cysteine Accessibility Method Analysis of Human Concentrative Nucleoside Transporter hCNT3 Reveals a Novel Discontinuous Region of Functional Importance within the CNT Family Motif (G/A)XKX3NEFVA(Y/M/F).

J Biol Chem, 284, 17281-17292.

19380587 M.D.Slugoski, K.M.Smith, A.M.Ng, S.Y.Yao, E.Karpinski, C.E.Cass, S.A.Baldwin, and J.D.Young (2009).
Conserved Glutamate Residues Glu-343 and Glu-519 Provide Mechanistic Insights into Cation/Nucleoside Cotransport by Human Concentrative Nucleoside Transporter hCNT3.

J Biol Chem, 284, 17266-17280.

19307590 M.Quick, A.M.Winther, L.Shi, P.Nissen, H.Weinstein, and J.A.Javitch (2009).
Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation.

Proc Natl Acad Sci U S A, 106, 5563-5568.

PDB codes: 3gjc 3gjd

19706416 M.S.Yousef, and L.Guan (2009).
A 3D structure model of the melibiose permease of Escherichia coli represents a distinctive fold for Na+ symporters.

Proc Natl Acad Sci U S A, 106, 15291-15296.

19608859 P.L.Shaffer, A.Goehring, A.Shankaranarayanan, and E.Gouaux (2009).
Structure and mechanism of a Na+-independent amino acid transporter.

Science, 325, 1010-1014.

PDB codes: 3gi8 3gi9 3gia

19449323 P.S.Kharkar, A.M.Batman, J.Zhen, P.M.Beardsley, M.E.Reith, and A.K.Dutta (2009).
Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

ChemMedChem, 4, 1075-1085.

19158093 Q.Zhu, R.Azimov, L.Kao, D.Newman, W.Liu, N.Abuladze, A.Pushkin, and I.Kurtz (2009).
NBCe1-A Transmembrane Segment 1 Lines the Ion Translocation Pathway.

J Biol Chem, 284, 8918-8929.

19429678 R.Valdés, S.Arastu-Kapur, S.M.Landfear, and U.Shinde (2009).
An ab Initio Structural Model of a Nucleoside Permease Predicts Functionally Important Residues.

J Biol Chem, 284, 19067-19076.

19472175 S.Bröer (2009).
The role of the neutral amino acid transporter B0AT1 (SLC6A19) in Hartnup disorder and protein nutrition.

IUBMB Life, 61, 591-599.

19199083 S.D.Robertson, H.J.Matthies, and A.Galli (2009).
A closer look at amphetamine-induced reverse transport and trafficking of the dopamine and norepinephrine transporters.

Mol Neurobiol, 39, 73-80.

19258316 S.H.Cho, and J.Beckwith (2009).
Two Snapshots of Electron Transport across the Membrane: INSIGHTS INTO THE STRUCTURE AND FUNCTION OF DsbD.

J Biol Chem, 284, 11416-11424.

19458709 S.H.White (2009).
Biophysical dissection of membrane proteins.

Nature, 459, 344-346.

19262666 S.Ressl, A.C.Terwisscha van Scheltinga, C.Vonrhein, V.Ott, and C.Ziegler (2009).
Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP.

Nature, 458, 47-52.

19478139 X.Gao, F.Lu, L.Zhou, S.Dang, L.Sun, X.Li, J.Wang, and Y.Shi (2009).
Structure and mechanism of an amino acid antiporter.

Science, 324, 1565-1568.

PDB codes: 3h5m 3h6b

19389778 Y.Kajiyama, M.Otagiri, J.Sekiguchi, T.Kudo, and S.Kosono (2009).
The MrpA, MrpB and MrpD subunits of the Mrp antiporter complex in Bacillus subtilis contain membrane-embedded and essential acidic residues.

Microbiology, 155, 2137-2147.

19430461 Z.Zhou, J.Zhen, N.K.Karpowich, C.J.Law, M.E.Reith, and D.N.Wang (2009).
Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.

Nat Struct Mol Biol, 16, 652-657.

18844672 A.M.Jørgensen, and S.Topiol (2008).
Driving forces for ligand migration in the leucine transporter.

Chem Biol Drug Des, 72, 265-272.

18381286 A.Rosenberg, and B.I.Kanner (2008).
The substrates of the gamma-aminobutyric acid transporter GAT-1 induce structural rearrangements around the interface of transmembrane domains 1 and 6.

J Biol Chem, 283, 14376-14383.

18668099 B.I.Kanner (2008).
Structural biology: It's not all in the family.

Nature, 454, 593-594.

18357440 B.Wenge, and H.Bönisch (2008).
N-Ethylmaleimide differentially inhibits substrate uptake by and ligand binding to the noradrenaline transporter.

Naunyn Schmiedebergs Arch Pharmacol, 377, 255-265.

18708457 D.A.Caplan, J.O.Subbotina, and S.Y.Noskov (2008).
Molecular mechanism of ion-ion and ion-substrate coupling in the Na+-dependent leucine transporter LeuT.

Biophys J, 95, 4613-4621.

18156179 D.Hilger, M.Böhm, A.Hackmann, and H.Jung (2008).
Role of Ser-340 and Thr-341 in transmembrane domain IX of the Na+/proline transporter PutP of Escherichia coli in ligand binding and transport.

J Biol Chem, 283, 4921-4929.

18209729 D.L.Murphy, and K.P.Lesch (2008).
Targeting the murine serotonin transporter: insights into human neurobiology.

Nat Rev Neurosci, 9, 85-96.

18819925 F.Casagrande, M.Ratera, A.D.Schenk, M.Chami, E.Valencia, J.M.Lopez, D.Torrents, A.Engel, M.Palacin, and D.Fotiadis (2008).
Projection structure of a member of the amino acid/polyamine/organocation transporter superfamily.

J Biol Chem, 283, 33240-33248.

18798526 F.Zafra, and C.Giménez (2008).
Glycine transporters and synaptic function.

IUBMB Life, 60, 810-817.

18203825 G.Christie, M.Lazarevska, and C.R.Lowe (2008).
Functional consequences of amino acid substitutions to GerVB, a component of the Bacillus megaterium spore germinant receptor.

J Bacteriol, 190, 2014-2022.

18252709 I.Bartholomäus, L.Milan-Lobo, A.Nicke, S.Dutertre, H.Hastrup, A.Jha, U.Gether, H.H.Sitte, H.Betz, and V.Eulenburg (2008).
Glycine transporter dimers: evidence for occurrence in the plasma membrane.

J Biol Chem, 283, 10978-10991.

18945273 I.H.Lambert, E.K.Hoffmann, and S.F.Pedersen (2008).
Cell volume regulation: physiology and pathophysiology.

Acta Physiol (Oxf), 194, 255-282.

18678877 I.H.Shrivastava, J.Jiang, S.G.Amara, and I.Bahar (2008).
Time-resolved Mechanism of Extracellular Gate Opening and Substrate Binding in a Glutamate Transporter.

J Biol Chem, 283, 28680-28690.

18542993 J.H.Jacobsen, C.A.Clement, M.B.Friis, and I.H.Lambert (2008).
Casein kinase 2 regulates the active uptake of the organic osmolyte taurine in NIH3T3 mouse fibroblasts.

Pflugers Arch, 457, 327-337.

18426798 J.Kniazeff, L.Shi, C.J.Loland, J.A.Javitch, H.Weinstein, and U.Gether (2008).
An intracellular interaction network regulates conformational transitions in the dopamine transporter.

J Biol Chem, 283, 17691-17701.

18197083 J.R.Wendland, T.B.DeGuzman, F.McMahon, G.Rudnick, S.D.Detera-Wadleigh, and D.L.Murphy (2008).
SERT Ileu425Val in autism, Asperger syndrome and obsessive-compulsive disorder.

Psychiatr Genet, 18, 31-39.

18266934 K.Severinsen, S.Sinning, H.K.Müller, and O.Wiborg (2008).
Characterisation of the zebrafish serotonin transporter functionally links TM10 to the ligand binding site.

J Neurochem, 105, 1794-1805.

18024499 L.Celik, B.Schiøtt, and E.Tajkhorshid (2008).
Substrate binding and formation of an occluded state in the leucine transporter.

Biophys J, 94, 1600-1612.

18772896 L.Csanády, and J.A.Mindell (2008).
The twain shall meet: channels, transporters and things between. Meeting on Membrane Transport in Flux: the Ambiguous Interface Between Channels and Pumps.

EMBO Rep, 9, 960-965.

18647834 L.R.Forrest, Y.W.Zhang, M.T.Jacobs, J.Gesmonde, L.Xie, B.H.Honig, and G.Rudnick (2008).
Mechanism for alternating access in neurotransmitter transporters.

Proc Natl Acad Sci U S A, 105, 10338-10343.

18199742 M.D.Slugoski, A.M.Ng, S.Y.Yao, K.M.Smith, C.C.Lin, J.Zhang, E.Karpinski, C.E.Cass, S.A.Baldwin, and J.D.Young (2008).
A proton-mediated conformational shift identifies a mobile pore-lining cysteine residue (Cys-561) in human concentrative nucleoside transporter 3.

J Biol Chem, 283, 8496-8507.

18628241 M.I.Torres-Altoro, K.J.White, G.J.Rodríguez, D.E.Nichols, and E.L.Barker (2008).
Helix XI contributes to the entrance of the serotonin transporter permeation pathway.

Protein Sci, 17, 1761-1770.

17847094 M.Indarte, J.D.Madura, and C.K.Surratt (2008).
Dopamine transporter comparative molecular modeling and binding site prediction using the LeuT(Aa) leucine transporter as a template.

Proteins, 70, 1033-1046.

18024501 N.Dave, V.A.Lórenz-Fonfría, G.Leblanc, and E.Padrós (2008).
FTIR spectroscopy of secondary-structure reorientation of melibiose permease modulated by substrate binding.

Biophys J, 94, 3659-3670.

18500332 N.H.Joh, A.Min, S.Faham, J.P.Whitelegge, D.Yang, V.L.Woods, and J.U.Bowie (2008).
Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins.

Nature, 453, 1266-1270.

PDB codes: 3coc 3cod

18946534 R.J.Harvey, E.Carta, B.R.Pearce, S.K.Chung, S.Supplisson, M.I.Rees, and K.Harvey (2008).
A critical role for glycine transporters in hyperexcitability disorders.

Front Mol Neurosci, 1, 1.

18715895 R.Mongeon, M.R.Gleason, M.A.Masino, J.R.Fetcho, G.Mandel, P.Brehm, and J.E.Dallman (2008).
Synaptic homeostasis in a zebrafish glial glycine transporter mutant.

J Neurophysiol, 100, 1716-1723.

19033659 S.Bröer, C.G.Bailey, S.Kowalczuk, C.Ng, J.M.Vanslambrouck, H.Rodgers, C.Auray-Blais, J.A.Cavanaugh, A.Bröer, and J.E.Rasko (2008).
Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters.

J Clin Invest, 118, 3881-3892.

18073211 S.Detro-Dassen, M.Schänzler, H.Lauks, I.Martin, S.M.zu Berstenhorst, D.Nothmann, D.Torres-Salazar, P.Hidalgo, G.Schmalzing, and C.Fahlke (2008).
Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion exchangers.

J Biol Chem, 283, 4177-4188.

18599740 S.Faham, A.Watanabe, G.M.Besserer, D.Cascio, A.Specht, B.A.Hirayama, E.M.Wright, and J.Abramson (2008).
The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport.

Science, 321, 810-814.

PDB code: 3dh4

19074341 S.K.Singh, C.L.Piscitelli, A.Yamashita, and E.Gouaux (2008).
A competitive inhibitor traps LeuT in an open-to-out conformation.

Science, 322, 1655-1661.

PDB codes: 3f3a 3f3c 3f3d 3f3e 3f48 3f4i 3f4j

18927357 S.Weyand, T.Shimamura, S.Yajima, S.Suzuki, O.Mirza, K.Krusong, E.P.Carpenter, N.G.Rutherford, J.M.Hadden, J.O'Reilly, P.Ma, M.Saidijam, S.G.Patching, R.J.Hope, H.T.Norbertczak, P.C.Roach, S.Iwata, P.J.Henderson, and A.D.Cameron (2008).
Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.

Science, 322, 709-713.

PDB codes: 2jln 2jlo

18536011 S.Y.Noskov (2008).
Molecular mechanism of substrate specificity in the bacterial neutral amino acid transporter LeuT.

Proteins, 73, 851-863.

18568020 T.Beuming, J.Kniazeff, M.L.Bergmann, L.Shi, L.Gracia, K.Raniszewska, A.H.Newman, J.A.Javitch, H.Weinstein, U.Gether, and C.J.Loland (2008).
The binding sites for cocaine and dopamine in the dopamine transporter overlap.

Nat Neurosci, 11, 780-789.

18293089 T.Nagata, S.Iizumi, K.Satoh, and S.Kikuchi (2008).
Comparative molecular biological analysis of membrane transport genes in organisms.

Plant Mol Biol, 66, 565-585.

18198474 T.Nakagawa, and S.Kaneko (2008).
Neuropsychotoxicity of Abused Drugs: Molecular and Neural Mechanisms of Neuropsychotoxicity Induced by Methamphetamine, 3,4-Methylenedioxymethamphetamine (Ecstasy), and 5-Methoxy-N,N-diisopropyltryptamine (Foxy).

J Pharmacol Sci, 106, 2-8.

18411273 Y.Y.Kim, D.Y.Kim, D.Shim, W.Y.Song, J.Lee, J.I.Schroeder, S.Kim, N.Moran, and Y.Lee (2008).
Expression of the novel wheat gene TM20 confers enhanced cadmium tolerance to bakers' yeast.

J Biol Chem, 283, 15893-15902.

17606623 A.De la Vieja, M.D.Reed, C.S.Ginter, and N.Carrasco (2007).
Amino acid residues in transmembrane segment IX of the Na+/I- symporter play a role in its Na+ dependence and are critical for transport activity.

J Biol Chem, 282, 25290-25298.

17311527 A.Kedrov, H.Janovjak, K.T.Sapra, and D.J.Müller (2007).
Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy.

Annu Rev Biophys Biomol Struct, 36, 233-260.

17994179 A.L.Gonzales, W.Lee, S.R.Spencer, R.A.Oropeza, J.V.Chapman, J.Y.Ku, and S.Eskandari (2007).
Turnover rate of the gamma-aminobutyric acid transporter GAT1.

J Membr Biol, 220, 33-51.

17436258 A.M.Jørgensen, L.Tagmose, A.M.Jørgensen, K.P.Bøgesø, and G.H.Peters (2007).
Molecular Dynamics Simulations of Na(+)/Cl(-)-Dependent Neurotransmitter Transporters in a Membrane-Aqueous System.

ChemMedChem, 2, 827-840.

17405130 A.M.Jørgensen, L.Tagmose, A.M.Jørgensen, S.Topiol, M.Sabio, K.Gundertofte, K.P.Bøgesø, and G.H.Peters (2007).
Homology Modeling of the Serotonin Transporter: Insights into the Primary Escitalopram-binding Site.

ChemMedChem, 2, 815-826.

17502375 B.Christiansen, A.K.Meinild, A.A.Jensen, and H.Braüner-Osborne (2007).
Cloning and characterization of a functional human gamma-aminobutyric acid (GABA) transporter, human GAT-2.

J Biol Chem, 282, 19331-19341.

17211682 C.J.De Feo, S.G.Aller, and V.M.Unger (2007).
A structural perspective on copper uptake in eukaryotes.

Biometals, 20, 705-716.

17941992 D.R.Livesay, P.D.Kidd, S.Eskandari, and U.Roshan (2007).
Assessing the ability of sequence-based methods to provide functional insight within membrane integral proteins: a case study analyzing the neurotransmitter/Na+ symporter family.

BMC Bioinformatics, 8, 397.

17704762 E.Zomot, A.Bendahan, M.Quick, Y.Zhao, J.A.Javitch, and B.I.Kanner (2007).
Mechanism of chloride interaction with neurotransmitter:sodium symporters.

Nature, 449, 726-730.

17428804 F.A.Paczkowski, I.A.Sharpe, S.Dutertre, and R.J.Lewis (2007).
chi-Conotoxin and tricyclic antidepressant interactions at the norepinephrine transporter define a new transporter model.

J Biol Chem, 282, 17837-17844.

17882334 F.Mancia, and W.A.Hendrickson (2007).
Expression of recombinant G-protein coupled receptors for structural biology.

Mol Biosyst, 3, 723-734.

17148440 H.P.Schneider, S.Bröer, A.Bröer, and J.W.Deitmer (2007).
Heterologous expression of the glutamine transporter SNAT3 in Xenopus oocytes is associated with four modes of uncoupled transport.

J Biol Chem, 282, 3788-3798.

17158291 H.W.Pinkett, A.T.Lee, P.Lum, K.P.Locher, and D.C.Rees (2007).
An inward-facing conformation of a putative metal-chelate-type ABC transporter.

Science, 315, 373-377.

PDB code: 2nq2

17186942 I.Giménez, and B.Forbush (2007).
The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2).

J Biol Chem, 282, 6540-6547.

17400549 J.R.Dodd, and D.L.Christie (2007).
Selective amino acid substitutions convert the creatine transporter to a gamma-aminobutyric acid transporter.

J Biol Chem, 282, 15528-15533.

17504760 J.Weerachayaphorn, and A.M.Pajor (2007).
Sodium-dependent extracellular accessibility of Lys-84 in the sodium/dicarboxylate cotransporter.

J Biol Chem, 282, 20213-20220.

17566106 L.Bamber, M.Harding, M.Monné, D.J.Slotboom, and E.R.Kunji (2007).
The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes.

Proc Natl Acad Sci U S A, 104, 10830-10834.

17059369 L.J.DeFelice, and T.Goswami (2007).
Transporters as channels.

Annu Rev Physiol, 69, 87.

17652169 L.R.Forrest, S.Tavoulari, Y.W.Zhang, G.Rudnick, and B.Honig (2007).
Identification of a chloride ion binding site in Na+/Cl -dependent transporters.

Proc Natl Acad Sci U S A, 104, 12761-12766.

17067279 M.K.Hahn, and R.D.Blakely (2007).
The functional impact of SLC6 transporter genetic variation.

Annu Rev Pharmacol Toxicol, 47, 401-441.

17079728 M.Miranda, K.R.Dionne, T.Sorkina, and A.Sorkin (2007).
Three ubiquitin conjugation sites in the amino terminus of the dopamine transporter mediate protein kinase C-dependent endocytosis of the transporter.

Mol Biol Cell, 18, 313-323.

17360689 M.Quick, and J.A.Javitch (2007).
Monitoring the function of membrane transport proteins in detergent-solubilized form.

Proc Natl Acad Sci U S A, 104, 3603-3608.

17255477 M.Rapp, S.Seppälä, E.Granseth, and G.von Heijne (2007).
Emulating membrane protein evolution by rational design.

Science, 315, 1282-1284.

17698848 M.T.Jacobs, Y.W.Zhang, S.D.Campbell, and G.Rudnick (2007).
Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter.

J Biol Chem, 282, 29441-29447.

17573427 M.Thomas, D.Jayatilaka, and B.Corry (2007).
The predominant role of coordination number in potassium channel selectivity.

Biophys J, 93, 2635-2643.

17230192 O.Boudker, R.M.Ryan, D.Yernool, K.Shimamoto, and E.Gouaux (2007).
Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter.

Nature, 445, 387-393.

PDB codes: 2nwl 2nww 2nwx

17415796 P.K.Thwar, B.Guptaroy, M.Zhang, M.E.Gnegy, M.A.Burns, and J.J.Linderman (2007).
Simple transporter trafficking model for amphetamine-induced dopamine efflux.

Synapse, 61, 500-514.

17255098 R.A.Vaughan, D.S.Sakrikar, M.L.Parnas, S.Adkins, J.D.Foster, R.A.Duval, J.R.Lever, S.S.Kulkarni, and A.Hauck-Newman (2007).
Localization of cocaine analog [125I]RTI 82 irreversible binding to transmembrane domain 6 of the dopamine transporter.

J Biol Chem, 282, 8915-8925.

17131045 R.Chen, H.Wei, E.R.Hill, L.Chen, L.Jiang, D.D.Han, and H.H.Gu (2007).
Direct evidence that two cysteines in the dopamine transporter form a disulfide bond.

Mol Cell Biochem, 298, 41-48.

17383967 R.J.Vandenberg, K.Shaddick, and P.Ju (2007).
Molecular basis for substrate discrimination by glycine transporters.

J Biol Chem, 282, 14447-14453.

17435767 R.M.Ryan, and J.A.Mindell (2007).
The uncoupled chloride conductance of a bacterial glutamate transporter homolog.

Nat Struct Mol Biol, 14, 365-371.

17443808 R.Romero-Calderón, R.M.Shome, A.F.Simon, R.W.Daniels, A.DiAntonio, and D.E.Krantz (2007).
A screen for neurotransmitter transporters expressed in the visual system of Drosophila melanogaster identifies three novel genes.

Dev Neurobiol, 67, 550-569.

17823609 S.G.Amara (2007).
Chloride finds its place in the transport cycle.

Nat Struct Mol Biol, 14, 792-794.

17687333 S.K.Singh, A.Yamashita, and E.Gouaux (2007).
Antidepressant binding site in a bacterial homologue of neurotransmitter transporters.

Nature, 448, 952-956.

PDB codes: 2q6h 2q72 2qb4 2qei

18257176 S.Kitayama, and T.Dohi (2007).
[New development in study of neurotransmitter transporters]

Nippon Yakurigaku Zasshi, 130, 443.

17310063 S.Ramamoorthy, D.J.Samuvel, E.R.Buck, G.Rudnick, and L.D.Jayanthi (2007).
Phosphorylation of threonine residue 276 is required for acute regulation of serotonin transporter by cyclic GMP.

J Biol Chem, 282, 11639-11647.

17704058 S.Y.Yao, A.M.Ng, M.D.Slugoski, K.M.Smith, R.Mulinta, E.Karpinski, C.E.Cass, S.A.Baldwin, and J.D.Young (2007).
Conserved glutamate residues are critically involved in Na+/nucleoside cotransport by human concentrative nucleoside transporter 1 (hCNT1).

J Biol Chem, 282, 30607-30617.

17662110 T.Hisamitsu, K.Yamada, T.Y.Nakamura, and S.Wakabayashi (2007).
Functional importance of charged residues within the putative intracellular loops in pH regulation by Na+/ H+ exchanger NHE1.

FEBS J, 274, 4326-4335.

17704152 X.Huang, and C.G.Zhan (2007).
How dopamine transporter interacts with dopamine: insights from molecular modeling and simulation.

Biophys J, 93, 3627-3639.

17389249 Z.Tao, and C.Grewer (2007).
Cooperation of the conserved aspartate 439 and bound amino acid substrate is important for high-affinity Na+ binding to the glutamate transporter EAAC1.

J Gen Physiol, 129, 331-344.

17690258 Z.Zhou, J.Zhen, N.K.Karpowich, R.M.Goetz, C.J.Law, M.E.Reith, and D.N.Wang (2007).
LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake.

Science, 317, 1390-1393.

PDB code: 2qju

16544108 A.Kedrov, and D.J.Müller (2006).
Characterizing folding, structure, molecular interactions and ligand gated activation of single sodium/proton antiporters.

Naunyn Schmiedebergs Arch Pharmacol, 372, 400-412.

17417704 B.I.Kanner (2006).
Structure and function of sodium-coupled GABA and glutamate transporters.

J Membr Biol, 213, 89.

16831195 D.Menaker, A.Bendahan, and B.I.Kanner (2006).
The substrate specificity of a neuronal glutamate transporter is determined by the nature of the coupling ion.

J Neurochem, 99, 20-28.

16672221 D.Rotem, S.Steiner-Mordoch, and S.Schuldiner (2006).
Identification of tyrosine residues critical for the function of an ion-coupled multidrug transporter.

J Biol Chem, 281, 18715-18722.

16267046 E.Di Cera (2006).
A structural perspective on enzymes activated by monovalent cations.

J Biol Chem, 281, 1305-1308.

16477015 E.Olkhova, C.Hunte, E.Screpanti, E.Padan, and H.Michel (2006).
Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications.

Proc Natl Acad Sci U S A, 103, 2629-2634.

17417703 G.Rudnick (2006).
Serotonin transporters--structure and function.

J Membr Biol, 213, 101-110.

17417701 H.Jung, T.Pirch, and D.Hilger (2006).
Secondary transport of amino acids in prokaryotes.

J Membr Biol, 213, 119-133.

16462808 J.U.Bowie (2006).
Flip-flopping membrane proteins.

Nat Struct Mol Biol, 13, 94-96.

17008722 K.J.White, P.D.Kiser, D.E.Nichols, and E.L.Barker (2006).
Engineered zinc-binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter.

Protein Sci, 15, 2411-2422.

16419070 L.Adamian, and J.Liang (2006).
Prediction of buried helices in multispan alpha helical membrane proteins.

Proteins, 63, 1-5.

16740633 L.D.Jayanthi, B.Annamalai, D.J.Samuvel, U.Gether, and S.Ramamoorthy (2006).
Phosphorylation of the norepinephrine transporter at threonine 258 and serine 259 is linked to protein kinase C-mediated transporter internalization.

J Biol Chem, 281, 23326-23340.

16446422 L.Guan, I.N.Smirnova, G.Verner, S.Nagamori, S.Nagamoni, and H.R.Kaback (2006).
Manipulating phospholipids for crystallization of a membrane transport protein.

Proc Natl Acad Sci U S A, 103, 1723-1726.

16272152 L.K.Henry, J.R.Field, E.M.Adkins, M.L.Parnas, R.A.Vaughan, M.F.Zou, A.H.Newman, and R.D.Blakely (2006).
Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants.

J Biol Chem, 281, 2012-2023.

16751771 M.I.Rees, K.Harvey, B.R.Pearce, S.K.Chung, I.C.Duguid, P.Thomas, S.Beatty, G.E.Graham, L.Armstrong, R.Shiang, K.J.Abbott, S.M.Zuberi, J.B.Stephenson, M.J.Owen, M.A.Tijssen, A.M.van den Maagdenberg, T.G.Smart, S.Supplisson, and R.J.Harvey (2006).
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease.

Nat Genet, 38, 801-806.

17417702 M.O'Mara, A.Oakley, and S.Bröer (2006).
Mechanism and putative structure of B(0)-like neutral amino acid transporters.

J Membr Biol, 213, 111-118.

16798738 M.Quick, H.Yano, N.R.Goldberg, L.Duan, T.Beuming, L.Shi, H.Weinstein, and J.A.Javitch (2006).
State-dependent conformations of the translocation pathway in the tyrosine transporter Tyt1, a novel neurotransmitter:sodium symporter from Fusobacterium nucleatum.

J Biol Chem, 281, 26444-26454.

16429150 M.Rapp, E.Granseth, S.Seppälä, and G.von Heijne (2006).
Identification and evolution of dual-topology membrane proteins.

Nat Struct Mol Biol, 13, 112-116.

16627568 M.Sala-Rabanal, D.D.Loo, B.A.Hirayama, E.Turk, and E.M.Wright (2006).
Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1.

J Physiol, 574, 149-166.

17003034 M.Soskine, S.Mark, N.Tayer, R.Mizrachi, and S.Schuldiner (2006).
On parallel and antiparallel topology of a homodimeric multidrug transporter.

J Biol Chem, 281, 36205-36212.

16923164 O.V.Mortensen, and S.G.Amara (2006).
Gain of function mutants reveal sites important for the interaction of the atypical inhibitors benztropine and bupropion with monoamine transporters.

J Neurochem, 98, 1531-1540.

16724276 P.W.McDonald, T.Jessen, J.R.Field, and R.D.Blakely (2006).
Dopamine signaling architecture in Caenorhabditis elegans.

Cell Mol Neurobiol, 26, 593-618.

16754872 R.Chen, M.R.Tilley, H.Wei, F.Zhou, F.M.Zhou, S.Ching, N.Quan, R.L.Stephens, E.R.Hill, T.Nottoli, D.D.Han, and H.H.Gu (2006).
Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter.

Proc Natl Acad Sci U S A, 103, 9333-9338.

17468961 R.J.O'Connell, C.Yuan, L.J.Johnston, O.Rinco, I.Probodh, and S.N.Treistman (2006).
Gating and conductance changes in BK(Ca) channels in bilayers are reciprocal.

J Membr Biol, 213, 143-153.

16501047 S.G.Aller, and V.M.Unger (2006).
Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture.

Proc Natl Acad Sci U S A, 103, 3627-3632.

16527819 V.M.Korkhov, M.Holy, M.Freissmuth, and H.H.Sitte (2006).
The conserved glutamate (Glu136) in transmembrane domain 2 of the serotonin transporter is required for the conformational switch in the transport cycle.

J Biol Chem, 281, 13439-13448.

17012318 X.León, R.Lemonnier, G.Leblanc, and E.Padrós (2006).
Changes in secondary structures and acidic side chains of melibiose permease upon cosubstrates binding.

Biophys J, 91, 4440-4449.

17008313 Y.W.Zhang, and G.Rudnick (2006).
The cytoplasmic substrate permeation pathway of serotonin transporter.

J Biol Chem, 281, 36213-36220.

16757479 Y.Zhou, E.Zomot, and B.I.Kanner (2006).
Identification of a lithium interaction site in the gamma-aminobutyric acid (GABA) transporter GAT-1.

J Biol Chem, 281, 22092-22099.

16353950 C.K.Surratt, O.T.Ukairo, and S.Ramanujapuram (2005).
Recognition of psychostimulants, antidepressants, and other inhibitors of synaptic neurotransmitter uptake by the plasma membrane monoamine transporters.

AAPS J, 7, E739-E751.

16322449 E.Gouaux, and R.Mackinnon (2005).
Principles of selective ion transport in channels and pumps.

Science, 310, 1461-1465.

16648940 F.Meier-Abt, Y.Mokrab, and K.Mizuguchi (2005).
Organic anion transporting polypeptides of the OATP/SLCO superfamily: identification of new members in nonmammalian species, comparative modeling and a potential transport mode.

J Membr Biol, 208, 213-227.

16339740 I.Sobczak, and J.S.Lolkema (2005).
The 2-hydroxycarboxylate transporter family: physiology, structure, and mechanism.

Microbiol Mol Biol Rev, 69, 665-695.

16109712 M.Miranda, C.C.Wu, T.Sorkina, D.R.Korstjens, and A.Sorkin (2005).
Enhanced ubiquitylation and accelerated degradation of the dopamine transporter mediated by protein kinase C.

J Biol Chem, 280, 35617-35624.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.