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Structure and mechanism of mitochondrial proton-translocating transhydrogenase

Nature.com

The structure of a mammalian proton-translocating transhydrogenase in various conformations is solved by cryo-electron microscopy, and a mechanism for the coupling process within the enzyme is proposed.

1.Jackson, J. B. A review of the binding-change mechanism for proton-translocating transhydrogenase. Biochim. Biophys. Acta. 1817, 18391846 (2012).
2.Sazanov, L. A. & Jackson, J. B. Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria. FEBS Lett. 344, 109116 (1994).
3.Meimaridou, E. et al. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat. Genet. 44, 740742 (2012).
4.Toye, A. A. et al. A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia48, 675686 (2005).
5.Leung, J. H. et al. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science347, 178181 (2015).
6.Jackson, J. B., Leung, J. H., Stout, C. D., Schurig-Briccio, L. A. & Gennis, R. B. Review and Hypothesis. New insights into the reaction mechanism of transhydrogenase: Swivelling the dIII component may gate the proton channel. FEBS Lett. 589, 20272033 (2015).
7.Li, S. et al. Nicotinamide nucleotide transhydrogenase-mediated redox homeostasis promotes tumor growth and metastasis in gastric cancer. Redox Biol. 18, 246255 (2018).
8.Santos, L. R. B. et al. NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic -cells. Mol. Metab. 6, 535547 (2017).
9.Nickel, A. G. et al. Reversal of mitochondrial transhydrogenase causes oxidative stress in heart failure. Cell Metab. 22, 472484 (2015).
10.Prasad, G. S., Sridhar, V., Yamaguchi, M., Hatefi, Y. & Stout, C. D. Crystal structure of transhydrogenase domain III at 1.2 Å resolution. Nat. Struct. Biol. 6, 11261131 (1999).
11.Cotton, N. P. J., White, S. A., Peake, S. J., McSweeney, S. & Jackson, J. B. The crystal structure of an asymmetric complex of the two nucleotide binding components of proton-translocating transhydrogenase. Structure9, 165176 (2001).
12.Sundaresan, V., Yamaguchi, M., Chartron, J. & Stout, C. D. Conformational change in the NADP(H) binding domain of transhydrogenase defines four states. Biochemistry42, 1214312153 (2003).
13.Johansson, T. et al. X-ray structure of domain I of the proton-pumping membrane protein transhydrogenase from Escherichia coli. J. Mol. Biol. 352, 299312 (2005).
14.Mather, O. C., Singh, A., van Boxel, G. I., White, S. A. & Jackson, J. B. Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase. Biochemistry43, 1095210964 (2004).
15.Yamaguchi, M., Wakabayashi, S. & Hatefi, Y. Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase: effect of substrates on the sensitivity of the enzyme to trypsin and identification of tryptic cleavage sites. Biochemistry29, 41364143 (1990).
16.Yamaguchi, M. & Hatefi, Y. Mitochondrial nicotinamide nucleotide transhydrogenase: NADPH binding increases and NADP binding decreases the acidity and susceptibility to modification of cysteine-893. Biochemistry28, 60506056 (1989).
17.Padayatti, P. S. et al. Critical role of water molecules in proton translocation by the membrane-bound transhydrogenase. Structure25, 11111119 (2017).
18.Glavas, N. A., Hou, C. & Bragg, P. D. Involvement of histidine-91 of the subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli. Biochemistry34, 76947702 (1995).
19.Venning, J. D., Peake, S. J., Quirk, P. G. & Jackson, J. B. Stopped-flow reaction kinetics of recombinant components of proton-translocating transhydrogenase with physiological nucleotides. J. Biol. Chem. 275, 1949019497 (2000).
20.Yamaguchi, M. & Hatefi, Y. High cyclic transhydrogenase activity catalyzed by expressed and reconstituted nucleotide-binding domains of Rhodospirillum rubrum transhydrogenase. Biochim. Biophys. Acta1318, 225234 (1997).
21.Venning, J. D., Bizouarn, T., Cotton, N. P. J., Quirk, P. G. & Jackson, J. B. Stopped-flow kinetics of hydride transfer between nucleotides by recombinant domains of proton-translocating transhydrogenase. Eur. J. Biochem. 257, 202209 (1998).
22.Fjellström, O., Johansson, C. & Rydström, J. Structural and catalytic properties of the expressed and purified NAD(H)- and NADP(H)-binding domains of proton-pumping transhydrogenase from Escherichia coli. Biochemistry36, 1133111341 (1997).
23.Bizouarn, T., van Boxel, G. I., Bhakta, T. & Jackson, J. B. Nucleotide binding affinities of the intact proton-translocating transhydrogenase from Escherichia coli. Biochim. Biophys. Acta1708, 404410 (2005).
24.Glavas, N. A. & Bragg, P. D. The mechanism of hydride transfer between NADH and 3-acetylpyridine adenine dinucleotide by the pyridine nucleotide transhydrogenase of Escherichia coli. Biochim. Biophys. Acta1231, 297303 (1995).
25.Sazanov, L. A. & Jackson, J. B. Cyclic reactions catalysed by detergent-dispersed and reconstituted transhydrogenase from beef-heart mitochondria; implications for the mechanism of proton translocation. Biochim. Biophys. Acta1231, 304312 (1995).
26.Hutton, M., Day, J. M., Bizouarn, T. & Jackson, J. B. Kinetic resolution of the reaction catalysed by proton-translocating transhydrogenase from Escherichia coli as revealed by experiments with analogues of the nucleotide substrates. Eur. J. Biochem. 219, 10411051 (1994).
27.Phelps, D. C. & Hatefi, Y. Interaction of purified nicotinamidenucleotide transhydrogenase with dicyclohexylcarbodiimide. Biochemistry23, 44754480 (1984).
28.Yamaguchi, M. & Hatefi, Y. Energy-transducing nicotinamide nucleotide transhydrogenase. Nucleotide binding properties of the purified enzyme and proteolytic fragments. J. Biol. Chem. 268, 1787117877 (1993).
29.Obiozo, U. M. et al. Substitution of tyrosine 146 in the dI component of proton-translocating transhydrogenase leads to reversible dissociation of the active dimer into inactive monomers. J. Biol. Chem. 282, 3643436443 (2007).
30.Fjellström, O. et al. Catalytic properties of hybrid complexes of the NAD(H)-binding and NADP(H)-binding domains of the proton-translocating transhydrogenases from Escherichia coli and Rhodospirillum rubrum. Biochemistry38, 415422 (1999).
31.Smith, A. L. Preparation, properties, and conditions for assay of mitochondria: Slaughterhouse material, small-scale. Methods Enzymol. 10, 8186 (1967).
32.Letts, J. A., Degliesposti, G., Fiedorczuk, K., Skehel, M. & Sazanov, L. A. Purification of ovine respiratory complex I results in a highly active and stable preparation. J. Biol. Chem. 291, 2465724675 (2016).
33.Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519530 (2012).
34.Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods14, 331332 (2017).
35.Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216221 (2015).
36.Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife7, e42166 (2018).
37.Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods11, 6365 (2014).
38.Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N. & Sternberg, M. J. E. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc. 10, 845858 (2015).
39.Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D66, 486501 (2010).
40.Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D66, 213221 (2010).
41.Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M. & Sazanov L. A. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Mol. Cell (in the press).
42.Vandock, K. P., Emerson, D. J., McLendon, K. E. & Rassman, A. A. Phospholipid dependence of the reversible, energy-linked, mitochondrial transhydrogenase in Manduca sexta. J. Membr. Biol. 242, 8994 (2011).
43.Hu, X., Zhang, J. W., Persson, A. & Rydström, J. Characterization of the interaction of NADH with proton pumping E. coli transhydrogenase reconstituted in the absence and in the presence of bacteriorhodopsin. Biochim. Biophys. Acta Bioenerg. 1229, 6472 (1995).
44.Tong, R. C. W., Glavas, N. A. & Bragg, P. D. Topological analysis of the pyridine nucleotide transhydrogenase of Escherichia coli using proteolytic enzymes. Biochim. Biophys. Acta1080, 1928 (1991).
45.Landau, M. et al. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 33, W299W302 (2005).
46.Zhang, L. & Hermans, J. Hydrophilicity of cavities in proteins. Proteins24, 433-438 (1996).
47.Pravda, L. et al. MOLEonline: a web-based tool for analyzing channels, tunnels and pores (2018 update). Nucleic Acids Res. 46, W368W373 (2018).
48.Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774797 (2007).
49.Krissinel, E. Crystal contacts as natures docking solutions. J. Comput. Chem. 31, 133143 (2010).
50.Barad, B. A. et al. EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat. Methods12, 943946 (2015).
51.Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D66, 1221 (2010).
52.Goujon, M. et al. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. 38, W695W699 (2010).
53.Larkin, M. A. et al. Clustal W and Clustal X version 2.0. Bioinformatics23, 29472948 (2007).
54.Pettersen, E. F. et al. UCSF Chimeraa visualization system for exploratory research and analysis. J. Comput. Chem. 25, 16051612 (2004).
55.Wu, L. N. Y., Alberta, J. A. & Fisher, R. R. Purification and reconstitution of bovine heart mitochondrial transhydrogenase. Methods Enzymol. 126, 353360 (1986).

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