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PDBsum entry 1okc
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Transport protein PDB id
1okc

 

 

 

 

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Contents
Protein chain
292 a.a. *
Ligands
CXT
CDL ×3
LDM ×2
PC1 ×4
Waters ×83
* Residue conservation analysis
PDB id:
1okc
Name: Transport protein
Title: Structure of mitochondrial adp/atp carrier in complex with carboxyatractyloside
Structure: Adp, atp carrier protein heart isoform t1. Chain: a. Synonym: adp/atp translocase 1, adenine nucleotide translocator 1, ant 1
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: heart. Tissue: muscle
Resolution:
2.20Å     R-factor:   0.220     R-free:   0.266
Authors: E.Pebay-Peyroula,C.Dahout-Gonzalez,R.Kahn,V.Trezeguet,G.J.-M.Lauquin, G.Brandolin
Key ref:
E.Pebay-Peyroula et al. (2003). Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature, 426, 39-44. PubMed id: 14603310 DOI: 10.1038/nature02056
Date:
21-Jul-03     Release date:   07-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P02722  (ADT1_BOVIN) -  ADP/ATP translocase 1 from Bos taurus
Seq:
Struc: 		298 a.a.
292 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1038/nature02056 Nature 426:39-44 (2003)
PubMed id: 14603310  
 
 
Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside.
E.Pebay-Peyroula, C.Dahout-Gonzalez, R.Kahn, V.Trézéguet, G.J.Lauquin, G.Brandolin.
 
  ABSTRACT  
 
ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 A by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six alpha-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers (RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a 'pit' to a 'channel' conformation.
 
  Selected figure(s)  
 
Figure 5.
Figure 5: The binding of CATR. a, Chemical formula of CATR. b, CATR within the binding pocket viewed from the outside. c, Electron density map at 2.2 Å resolution (2F[obs] - F[calc], contoured at 1 obtained before CATR modelling and including only protein atoms) around CATR. Residues directly within hydrogen-bond distances to CATR are labelled. Black arrowheads indicate van der Waals contacts between CATR and the protein. d, A close-up of the two CATR carboxylates interacting with arginines. Interatomic distances are given in Å. 		Figure 6.
Figure 6: The closed conformation of the carrier viewed from the matrix. Only odd-numbered helices are represented. Residues involved in the PX(D/E)XX(K/R) sequence are labelled. Black lines connect atoms within hydrogen-bonding distances (in Å).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 426, 39-44) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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Rows of ATP synthase dimers in native mitochondrial inner membranes.
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17961500 N.Giangregorio, A.Tonazzi, C.Indiveri, and F.Palmieri (2007).
Conformation-dependent accessibility of Cys-136 and Cys-155 of the mitochondrial rat carnitine/acylcarnitine carrier to membrane-impermeable SH reagents.
  Biochim Biophys Acta, 1767, 1331-1339.  
17596519 S.Floyd, C.Favre, F.M.Lasorsa, M.Leahy, G.Trigiante, P.Stroebel, A.Marx, G.Loughran, K.O'Callaghan, C.M.Marobbio, D.J.Slotboom, E.R.Kunji, F.Palmieri, and R.O'Connor (2007).
The insulin-like growth factor-I-mTOR signaling pathway induces the mitochondrial pyrimidine nucleotide carrier to promote cell growth.
  Mol Biol Cell, 18, 3545-3555.  
17452106 S.Schuldiner (2007).
When biochemistry meets structural biology: the cautionary tale of EmrE.
  Trends Biochem Sci, 32, 252-258.  
17261580 S.Thuswaldner, J.O.Lagerstedt, M.Rojas-Stütz, K.Bouhidel, C.Der, N.Leborgne-Castel, A.Mishra, F.Marty, B.Schoefs, I.Adamska, B.L.Persson, and C.Spetea (2007).
Identification, expression, and functional analyses of a thylakoid ATP/ADP carrier from Arabidopsis.
  J Biol Chem, 282, 8848-8859.  
17263664 W.Neupert, and J.M.Herrmann (2007).
Translocation of proteins into mitochondria.
  Annu Rev Biochem, 76, 723-749.  
17137571 Y.H.Kim, G.Haidl, M.Schaefer, U.Egner, A.Mandal, and J.C.Herr (2007).
Compartmentalization of a unique ADP/ATP carrier protein SFEC (Sperm Flagellar Energy Carrier, AAC4) with glycolytic enzymes in the fibrous sheath of the human sperm flagellar principal piece.
  Dev Biol, 302, 463-476.  
17473430 Y.Kihira, M.Ueno, and H.Terada (2007).
Difference between yeast and bovine mitochondrial ADP/ATP carriers in terms of conformational properties of the first matrix loop as deduced by use of copper-o-phenanthroline.
  Biol Pharm Bull, 30, 885-890.  
16469842 A.J.Robinson, and E.R.Kunji (2006).
Mitochondrial carriers in the cytoplasmic state have a common substrate binding site.
  Proc Natl Acad Sci U S A, 103, 2617-2622.  
16761086 A.Y.Mulkidjanian, and D.A.Cherepanov (2006).
Probing biological interfaces by tracing proton passage across them.
  Photochem Photobiol Sci, 5, 577-587.  
16986324 A.Ziemys, A.Toleikis, and D.M.Kopustinskiene (2006).
Molecular modelling of K(ATP) channel blockers-ADP/ ATP carrier interactions.
  Syst Biol (Stevenage), 153, 390-393.  
16896205 C.Colasante, V.P.Alibu, S.Kirchberger, J.Tjaden, C.Clayton, and F.Voncken (2006).
Characterization and developmentally regulated localization of the mitochondrial carrier protein homologue MCP6 from Trypanosoma brucei.
  Eukaryot Cell, 5, 1194-1205.  
16387659 C.T.Webb, M.A.Gorman, M.Lazarou, M.T.Ryan, and J.M.Gulbis (2006).
Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller.
  Mol Cell, 21, 123-133.
PDB code: 2bsk
16616497 C.de Marcos-Lousa, D.P.Sideris, and K.Tokatlidis (2006).
Translocation of mitochondrial inner-membrane proteins: conformation matters.
  Trends Biochem Sci, 31, 259-267.  
16903835 D.V.Mamaev, D.A.Aliverdieva, D.I.Bondarenko, and K.F.Sholtz (2006).
Study of active site topography of rat liver mitochondrial dicarboxylate transporter using lipophilic substrate derivatives.
  Biochemistry (Mosc), 71, 800-809.  
16239329 E.Metelkin, I.Goryanin, and O.Demin (2006).
Mathematical modeling of mitochondrial adenine nucleotide translocase.
  Biophys J, 90, 423-432.  
16492162 E.N.Sabbah, S.Druillennec, N.Morellet, S.Bouaziz, G.Kroemer, and B.P.Roques (2006).
Interaction between the HIV-1 protein Vpr and the adenine nucleotide translocator.
  Chem Biol Drug Des, 67, 145-154.
PDB codes: 1ym6 1ymj
16451122 H.Nury, C.Dahout-Gonzalez, V.Trézéguet, G.J.Lauquin, G.Brandolin, and E.Pebay-Peyroula (2006).
Relations between structure and function of the mitochondrial ADP/ATP carrier.
  Annu Rev Biochem, 75, 713-741.  
17056710 L.Bamber, M.Harding, P.J.Butler, and E.R.Kunji (2006).
Yeast mitochondrial ADP/ATP carriers are monomeric in detergents.
  Proc Natl Acad Sci U S A, 103, 16224-16229.  
16988954 M.Falconi, G.Chillemi, D.Di Marino, I.D'Annessa, B.Morozzo della Rocca, L.Palmieri, and A.Desideri (2006).
Structural dynamics of the mitochondrial ADP/ATP carrier revealed by molecular dynamics simulation studies.
  Proteins, 65, 681-691.  
16407270 S.Sunderhaus, N.V.Dudkina, L.Jänsch, J.Klodmann, J.Heinemeyer, M.Perales, E.Zabaleta, E.J.Boekema, and H.P.Braun (2006).
Carbonic anhydrase subunits form a matrix-exposed domain attached to the membrane arm of mitochondrial complex I in plants.
  J Biol Chem, 281, 6482-6488.  
16641489 T.Páli, D.Bashtovyy, and D.Marsh (2006).
Stoichiometry of lipid interactions with transmembrane proteins--Deduced from the 3D structures.
  Protein Sci, 15, 1153-1161.  
17008313 Y.W.Zhang, and G.Rudnick (2006).
The cytoplasmic substrate permeation pathway of serotonin transporter.
  J Biol Chem, 281, 36213-36220.  
  16316975 A.Accardi, M.Walden, W.Nguitragool, H.Jayaram, C.Williams, and C.Miller (2005).
Separate ion pathways in a Cl-/H+ exchanger.
  J Gen Physiol, 126, 563-570.
PDB codes: 2fec 2fed 2fee
15647764 A.Flierl, Y.Chen, P.E.Coskun, R.J.Samulski, and D.C.Wallace (2005).
Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse.
  Gene Ther, 12, 570-578.  
15809292 A.Haguenauer, S.Raimbault, S.Masscheleyn, M.d.e.l. .M.Gonzalez-Barroso, F.Criscuolo, J.Plamondon, B.Miroux, D.Ricquier, D.Richard, F.Bouillaud, and C.Pecqueur (2005).
A new renal mitochondrial carrier, KMCP1, is up-regulated during tubular cell regeneration and induction of antioxidant enzymes.
  J Biol Chem, 280, 22036-22043.  
16172928 A.J.Watson, A.V.Hughes, P.K.Fyfe, M.C.Wakeham, K.Holden-Dye, P.Heathcote, and M.R.Jones (2005).
On the role of basic residues in adapting the reaction centre-LH1 complex for growth at elevated temperatures in purple bacteria.
  Photosynth Res, 86, 81.  
15862092 A.P.Weber, R.Schwacke, and U.I.Flügge (2005).
Solute transporters of the plastid envelope membrane.
  Annu Rev Plant Biol, 56, 133-164.  
15757911 A.Tonazzi, N.Giangregorio, C.Indiveri, and F.Palmieri (2005).
Identification by site-directed mutagenesis and chemical modification of three vicinal cysteine residues in rat mitochondrial carnitine/acylcarnitine transporter.
  J Biol Chem, 280, 19607-19612.
PDB code: 2bmn
16308278 B.Morozzo Della Rocca, D.V.Miniero, G.Tasco, V.Dolce, M.Falconi, A.Ludovico, A.R.Cappello, P.Sanchez, I.Stipani, R.Casadio, A.Desideri, and F.Palmieri (2005).
Substrate-induced conformational changes of the mitochondrial oxoglutarate carrier: a spectroscopic and molecular modelling study.
  Mol Membr Biol, 22, 443-452.  
15988517 C.Hunte, E.Screpanti, M.Venturi, A.Rimon, E.Padan, and H.Michel (2005).
Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH.
  Nature, 435, 1197-1202.
PDB code: 1zcd
15498760 C.Ma, R.Kotaria, J.A.Mayor, S.Remani, D.E.Walters, and R.S.Kaplan (2005).
The yeast mitochondrial citrate transport protein: characterization of transmembrane domain III residue involvement in substrate translocation.
  J Biol Chem, 280, 2331-2340.  
16475085 F.Criscuolo, M.d.e.l. .M.Gonzalez-Barroso, F.Bouillaud, D.Ricquier, B.Miroux, and G.Sorci (2005).
Mitochondrial uncoupling proteins: new perspectives for evolutionary ecologists.
  Am Nat, 166, 686-699.  
16339740 I.Sobczak, and J.S.Lolkema (2005).
The 2-hydroxycarboxylate transporter family: physiology, structure, and mechanism.
  Microbiol Mol Biol Rev, 69, 665-695.  
16249673 J.Feng, E.Lucchinetti, P.Ahuja, T.Pasch, J.C.Perriard, and M.Zaugg (2005).
Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3beta.
  Anesthesiology, 103, 987-995.  
15937550 J.G.Weaver, A.Tarze, T.C.Moffat, M.Lebras, A.Deniaud, C.Brenner, G.D.Bren, M.Y.Morin, B.N.Phenix, L.Dong, S.X.Jiang, V.L.Sim, B.Zurakowski, J.Lallier, H.Hardin, P.Wettstein, R.P.van Heeswijk, A.Douen, R.T.Kroemer, S.T.Hou, S.A.Bennett, D.H.Lynch, G.Kroemer, and A.D.Badley (2005).
Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor.
  J Clin Invest, 115, 1828-1838.  
16283555 J.Mozo, Y.Emre, F.Bouillaud, D.Ricquier, and F.Criscuolo (2005).
Thermoregulation: what role for UCPs in mammals and birds?
  Biosci Rep, 25, 227-249.  
16096261 J.S.Lolkema, and D.J.Slotboom (2005).
Sequence and hydropathy profile analysis of two classes of secondary transporters.
  Mol Membr Biol, 22, 177-189.  
15591051 K.Brandner, P.Rehling, and K.N.Truscott (2005).
The carboxyl-terminal third of the dicarboxylate carrier is crucial for productive association with the inner membrane twin-pore translocase.
  J Biol Chem, 280, 6215-6221.  
16015376 K.R.Vinothkumar, S.H.Smits, and W.Kühlbrandt (2005).
pH-induced structural change in a sodium/proton antiporter from Methanococcus jannaschii.
  EMBO J, 24, 2720-2729.  
15854906 K.W.Chan, D.J.Slotboom, S.Cox, T.M.Embley, O.Fabre, M.van der Giezen, M.Harding, D.S.Horner, E.R.Kunji, G.León-Avila, and J.Tovar (2005).
A novel ADP/ATP transporter in the mitosome of the microaerophilic human parasite Entamoeba histolytica.
  Curr Biol, 15, 737-742.  
15789404 L.Adamian, V.Nanda, W.F.DeGrado, and J.Liang (2005).
Empirical lipid propensities of amino acid residues in multispan alpha helical membrane proteins.
  Proteins, 59, 496-509.  
16096262 M.A.Castiglione-Morelli, A.Ostuni, F.Croce, F.Palmieri, and F.Bisaccia (2005).
Solution structure of the fifth and sixth transmembrane segments of the mitochondrial oxoglutarate carrier.
  Mol Membr Biol, 22, 191-201.  
16055441 M.Bedhomme, M.Hoffmann, E.A.McCarthy, B.Gambonnet, R.G.Moran, F.Rébeillé, and S.Ravanel (2005).
Folate metabolism in plants: an Arabidopsis homolog of the mammalian mitochondrial folate transporter mediates folate import into chloroplasts.
  J Biol Chem, 280, 34823-34831.  
16087876 M.Jidenko, R.C.Nielsen, T.L.Sørensen, J.V.Møller, M.le Maire, P.Nissen, and C.Jaxel (2005).
Crystallization of a mammalian membrane protein overexpressed in Saccharomyces cerevisiae.
  Proc Natl Acad Sci U S A, 102, 11687-11691.  
15688220 M.Mentel, J.Piskur, C.Neuvéglise, A.Rycovská, G.Cellengová, and J.Kolarov (2005).
Triplicate genes for mitochondrial ADP/ATP carriers in the aerobic yeast Yarrowia lipolytica are regulated differentially in the absence of oxygen.
  Mol Genet Genomics, 273, 84-91.  
16260761 M.Monné, K.W.Chan, D.J.Slotboom, and E.R.Kunji (2005).
Functional expression of eukaryotic membrane proteins in Lactococcus lactis.
  Protein Sci, 14, 3048-3056.  
16234568 P.J.Dilda, A.S.Don, K.M.Tanabe, V.J.Higgins, J.D.Allen, I.W.Dawes, and P.J.Hogg (2005).
Mechanism of selectivity of an angiogenesis inhibitor from screening a genome-wide set of Saccharomyces cerevisiae deletion strains.
  J Natl Cancer Inst, 97, 1539-1547.  
15738989 S.Krauss, C.Y.Zhang, and B.B.Lowell (2005).
The mitochondrial uncoupling-protein homologues.
  Nat Rev Mol Cell Biol, 6, 248-261.  
15994310 Y.W.Zhang, and G.Rudnick (2005).
Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2 suggests an alpha-helical conformation.
  J Biol Chem, 280, 30807-30813.  
15341730 A.Holmner, M.Lebens, S.Teneberg, J.Angström, M.Okvist, and U.Krengel (2004).
Novel binding site identified in a hybrid between cholera toxin and heat-labile enterotoxin: 1.9 A crystal structure reveals the details.
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PDB codes: 1tl0 2nzg 3efx
15332302 A.P.Halestrap (2004).
Mitochondrial permeability: dual role for the ADP/ATP translocator?
  Nature, 430, 1 p following 983.  
14976187 B.Faustin, R.Rossignol, C.Rocher, G.Bénard, M.Malgat, and T.Letellier (2004).
Mobilization of adenine nucleotide translocators as molecular bases of the biochemical threshold effect observed in mitochondrial diseases.
  J Biol Chem, 279, 20411-20421.  
15166242 C.Chen, Y.Ko, M.Delannoy, S.J.Ludtke, W.Chiu, and P.L.Pedersen (2004).
Mitochondrial ATP synthasome: three-dimensional structure by electron microscopy of the ATP synthase in complex formation with carriers for Pi and ADP/ATP.
  J Biol Chem, 279, 31761-31768.  
15298898 D.E.Walters, and R.S.Kaplan (2004).
Homology-modeled structure of the yeast mitochondrial citrate transport protein.
  Biophys J, 87, 907-911.  
15313235 E.Pebay-Peyroula, and G.Brandolin (2004).
Nucleotide exchange in mitochondria: insight at a molecular level.
  Curr Opin Struct Biol, 14, 420-425.  
15313233 M.J.Lemieux, Y.Huang, and D.N.Wang (2004).
The structural basis of substrate translocation by the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily.
  Curr Opin Struct Biol, 14, 405-412.  
15210985 P.M.Hwang, R.E.Bishop, and L.E.Kay (2004).
The integral membrane enzyme PagP alternates between two dynamically distinct states.
  Proc Natl Acad Sci U S A, 101, 9618-9623.  
15232570 P.Rehling, K.Brandner, and N.Pfanner (2004).
Mitochondrial import and the twin-pore translocase.
  Nat Rev Mol Cell Biol, 5, 519-530.  
15238515 X.J.Chen (2004).
Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae.
  Genetics, 167, 607-617.  
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 code is shown on the right.

 

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