Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport

Nature Structural and Molecular Biology

Volumn 21, Issue 11, 2014, Pages 990-996

  Ehrnstorfer, Ines A ^a   Geertsma, Eric R ^a,d   Pardon, Els ^b,c   Steyaert, Jan ^b,c   Dutzler, Raimund ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^d GOETHE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CADMIUM; CALCIUM ION; FERROUS ION; MANGANESE; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; AMINO ACID TRANSPORTER; BACTERIAL PROTEIN; CATION TRANSPORT PROTEIN; DIVALENT CATION; DMRT1 PROTEIN; IRON; NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 1; PROTEIN BINDING; RECOMBINANT PROTEIN; TRANSCRIPTION FACTOR;

ARTICLE; BINDING SITE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ION TRANSPORT; MOLECULAR INTERACTION; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN STRUCTURE; AMINO ACID SEQUENCE; CHEMICAL STRUCTURE; CHEMISTRY; ENZYME SPECIFICITY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; HUMAN; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; STAPHYLOCOCCUS; STRUCTURAL HOMOLOGY; X RAY CRYSTALLOGRAPHY;

PROKARYOTA; STAPHYLOCOCCUS CAPITIS;

AMINO ACID SEQUENCE; AMINO ACID TRANSPORT SYSTEMS; BACTERIAL PROTEINS; BINDING SITES; CADMIUM; CATION TRANSPORT PROTEINS; CATIONS, DIVALENT; CONSERVED SEQUENCE; CRYSTALLOGRAPHY, X-RAY; ESCHERICHIA COLI; GENE EXPRESSION; HUMANS; ION TRANSPORT; IRON; MANGANESE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEIN CONFORMATION; RECOMBINANT PROTEINS; STAPHYLOCOCCUS; STRUCTURAL HOMOLOGY, PROTEIN; SUBSTRATE SPECIFICITY; TRANSCRIPTION FACTORS;

EID: 84908885748     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2904     Document Type: Article

References (59)

1. Nevo, Y. &Nelson, N. The NRAMP family of metal-ion transporters. Biochim. Biophys. Acta 1763, 609-620 (2006).
2. Montalbetti, N., Simonin, A., Kovacs, G. &Hediger, M.A. Mammalian iron transporters: families SLC11 and SLC40. Mol. Aspects Med. 34, 270-287 (2013).
3. Cellier, M.F., Bergevin, I., Boyer, E. &Richer, E. Polyphyletic origins of bacterial Nramp transporters. Trends Genet. 17, 365-370 (2001).
4. Vidal, S.M., Malo, D., Vogan, K., Skamene, E. &Gros, P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73, 469-485 (1993).
5. Illing, A.C., Shawki, A., Cunningham, C.L. &Mackenzie, B. Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1. J. Biol. Chem. 287, 30485-30496 (2012).
6. Vidal, S.M., Pinner, E., Lepage, P., Gauthier, S. &Gros, P. Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse strains. J. Immunol. 157, 3559-3568 (1996).
7. Gunshin, H. et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482-488 (1997).
8. Beaumont, C. et al. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood 107, 4168-4170 (2006).
9. Johnson, E.E. &Wessling-Resnick, M. Iron metabolism and the innate immune response to infection. Microbes Infect. 14, 207-216 (2012).
10. Shawki, A., Knight, P.B., Maliken, B.D., Niespodzany, E.J. &Mackenzie, B.H. H+-coupled divalent metal-ion transporter-1: functional properties, physiological roles and therapeutics. Curr. Top. Membr. 70, 169-214 (2012).
11. Mackenzie, B., Ujwal, M.L., Chang, M.H., Romero, M.F. &Hediger, M.A. Divalent metal-ion transporter DMT1 mediates both H+-coupled Fe2+ transport and uncoupled fluxes. Pflugers Arch. 451, 544-558 (2006).
12. Shawki, A. &Mackenzie, B. Interaction of calcium with the human divalent metal-ion transporter-1. Biochem. Biophys. Res. Commun. 393, 471-475 (2010).
13. Au, C., Benedetto, A. &Aschner, M. Manganese transport in eukaryotes: the role of DMT1. Neurotoxicology 29, 569-576 (2008).
14. Bressler, J.P., Olivi, L., Cheong, J.H., Kim, Y. &Bannona, D. Divalent metal transporter 1 in lead and cadmium transport. Ann. NY Acad. Sci. 1012, 142-152 (2004).
15. Guerinot, M.L. Microbial iron transport. Annu. Rev. Microbiol. 48, 743-772 (1994).
16. Makui, H. et al. Identification of the Escherichia coli K-12 Nramp orthologue (MntH) as a selective divalent metal ion transporter. Mol. Microbiol. 35, 1065-1078 (2000).
17. Czachorowski, M., Lam-Yuk-Tseung, S., Cellier, M. &Gros, P. Transmembrane topology of the mammalian Slc11a2 iron transporter. Biochemistry 48, 8422-8434 (2009).
18. Yamashita, A., Singh, S.K., Kawate, T., Jin, Y. &Gouaux, E. Crystal structure of a bacterial homologue of Na+/Cl-dependent neurotransmitter transporters. Nature 437, 215-223 (2005).
19. Cellier, M.F. Nramp: from sequence to structure and mechanism of divalent metal import. Curr. Top. Membr. 69, 249-293 (2012).
20. Cellier, M.F. Nutritional immunity: homology modeling of Nramp metal import. Adv. Exp. Med. Biol. 946, 335-351 (2012).
21. Geertsma, E.R. &Dutzler, R. A versatile and efficient high-throughput cloning tool for structural biology. Biochemistry 50, 3272-3278 (2011).
22. Pardon, E. et al. A general protocol for the generation of Nanobodies for structural biology. Nat. Protoc. 9, 674-693 (2014).
23. Schulze, S., Koster, S., Geldmacher, U., Terwisscha van Scheltinga, A.C. &Kuhlbrandt, W. Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT. Nature 467, 233-236 (2010).
24. Ressl, S., Terwisscha van Scheltinga, A.C., Vonrhein, C., Ott, V. &Ziegler, C. Molecular basis of transport and regulation in the Na+/betaine symporter BetP. Nature 458, 47-52 (2009).
25. Weyand, S. et al. Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter. Science 322, 709-713 (2008).
26. Faham, S. et al. The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science 321, 810-814 (2008).
27. Gao, X. et al. Structure and mechanism of an amino acid antiporter. Science 324, 1565-1568 (2009).
28. Fang, Y. et al. Structure of a prokaryotic virtual proton pump at 3.2 resolution. Nature 460, 1040-1043 (2009).
29. Krishnamurthy, H. &Gouaux, E. X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481, 469-474 (2012).
30. Lam-Yuk-Tseung, S., Govoni, G., Forbes, J. &Gros, P. Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in transmembrane domain 6. Blood 101, 3699-3707 (2003).
31. Edward, R.A., Whittaker, M.M., Whittaker, J.W., Jameson, G.B. &Baker, E.N. Distinct metal environment in Fe-substituted manganese superoxide dismutatse provides a structural basis of metal specificity. J. Am. Chem. Soc. 120, 9684-9685 (1998).
32. Qi, W. &Cowan, J.A. Structural, mechanistic and coordination chemistry of relevance to the biosynthesis of iron-sulfur and related iron cofactors. Coord. Chem. Rev. 255, 688-699 (2011).
33. Freisinger, E. &Vasak, M. Cadmium in metallothioneins. Met. Ions. Life Sci. 11, 339-371 (2013).
34. Hoch, E. et al. Histidine pairing at the metal transport site of mammalian ZnT transporters controls Zn2+ over Cd2+ selectivity. Proc. Natl. Acad. Sci. USA 109, 7202-7207 (2012).
35. Cellier, M. et al. Nramp defines a family of membrane proteins. Proc. Natl. Acad. Sci. USA 92, 10089-10093 (1995).
36. Courville, P. et al. Solute carrier 11 cation symport requires distinct residues in transmembrane helices 1 and 6. J. Biol. Chem. 283, 9651-9658 (2008).
37. Haemig, H.A. &Brooker, R.J. Importance of conserved acidic residues in mntH, the Nramp homolog of Escherichia coli. J. Membr. Biol. 201, 97-107 (2004).
38. Haemig, H.A., Moen, P.J. &Brooker, R.J. Evidence that highly conserved residues of transmembrane segment 6 of Escherichia coli MntH are important for transport activity. Biochemistry 49, 4662-4671 (2010).
39. Xu, H., Jin, J., DeFelice, L.J., Andrews, N.C. &Clapham, D.E. A spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway. PLoS Biol. 2, E50 (2004).
40. Iolascon, A. &De Falco, L. Mutations in the gene encoding DMT1: clinical presentation and treatment. Semin. Hematol. 46, 358-370 (2009).
41. Courville, P., Chaloupka, R. &Cellier, M.F. Recent progress in structure-function analyses of Nramp proton-dependent metal-ion transporters. Biochem. Cell Biol. 84, 960-978 (2006).
42. Forrest, L.R. et al. Mechanism for alternating access in neurotransmitter transporters. Proc. Natl. Acad. Sci. USA 105, 10338-10343 (2008).
43. Casadaban, M.J. &Cohen, S.N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J. Mol. Biol. 138, 179-207 (1980).
44. Kawate, T. &Gouaux, E. Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. Structure 14, 673-681 2006).
45. Van Duyne, G.D., Standaert, R.F., Karplus, P.A., Schreiber, S.L. &Clardy, J. Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin. J. Mol. Biol. 229, 105-124 (1993).
46. Kabsch, W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Crystallogr. 26, 795-800 (1993).
47. Collaborative Computational Project, Number 4. The CCP4 Suite: programs for X-ray crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-763 (1994).
48. Schneider, T.R. &Sheldrick, G.M. Substructure solution with SHELXD. Acta Crystallogr. D Biol. Crystallogr. 58, 1772-1779 (2002).
49. Pape, T. &Schneider, T.R. HKL2MAP: a graphical user interface for phasing with SHELX programs. J. Appl. Crystallogr. 37, 843-844 (2004).
50. De La Fortelle, E. &Bricogne, G. Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. Methods Enzymol. 276, 472-494 (1997).
51. Cowtan, K. dm: an automated procedure for phase improvement by density modification. Joint CCP4 and ESF-EACBM Newslett. Protein Crystallogr. 31, 34-38 (1994).
52. Jones, T.A., Zou, J.Y., Cowan, S.W. &Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110-119 (1991).
53. Emsley, P. &Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).
54. Brnger, A.T. et al. Crystallography &NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54, 905-921 (1998).
55. Adams, P.D. et al. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr. 58, 1948-1954 (2002).
56. McCoy, A.J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
57. Geertsma, E.R., Nik Mahmood, N.A., Schuurman-Wolters, G.K. &Poolman, B. Membrane reconstitution of ABC transporters and assays of translocator function. Nat. Protoc. 3, 256-266 (2008).
58. Keller, S. et al. High-precision isothermal titration calorimetry with automated peak-shape analysis. Anal. Chem. 84, 5066-5073 (2012).
59. Lorenz, C., Pusch, M. &Jentsch, T.J. Heteromultimeric CLC chloride channels with novel properties. Proc. Natl. Acad. Sci. USA 93, 13362-13366 (1996).