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ESEEM Reveals Bound Substrate Histidine in the ABC Transporter HisQMP2

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Abstract

Localization of substrates in membrane proteins is an important but challenging task. In this paper, we show that deuterium electron spin echo envelope modulation spectroscopy (2H ESEEM) combined with site-directed spin labeling is a powerful tool to localize the substrate, histidine-d5, in the ABC transporter HisQMP2. Based on a homology model and spin label rotamer analyses, we calculated 2H ESEEM spectra for eight possible labeling positions close to the putative substrate-binding site. Experimental 2H ESEEM spectra were determined with spin labels bound either at position 169 of HisM, for which a detectable 2H ESEEM signal was calculated, or with a spin label bound at position 54 of HisQ as a negative control. The agreement between the calculated and experimental ESEEM spectra provides strong evidence for the histidine located in a binding site primarily liganded by residues of HisM as proposed by the homology model.

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References

  1. R. Santos, O. Ursu, A. Gaulton, A.P. Bento, R.S. Donadi, C.G. Bologa, A. Karlsson, B. Al-Lazikani, A. Hersey, T.I. Oprea, J.P. Overington, Nat. Rev. Drug Discov. 16, 19 (2017)

    Article  Google Scholar 

  2. M. Caffrey, Acta Crystallogr. Sect. FStructural Biol. Commun. 71, 3 (2015)

    Article  Google Scholar 

  3. Y. Cheng, Cell 161, 450 (2015)

    Article  Google Scholar 

  4. B. Liang, L.K. Tamm, Nat. Struct. Mol. Biol. 23, 468 (2016)

    Article  Google Scholar 

  5. N. Cox, A. Nalepa, M.-E. Pandelia, W. Lubitz, A. Savitsky, Methods Enzymol. 563, 211 (2015)

    Article  Google Scholar 

  6. G.E. Cutsail, J. Telser, B.M. Hoffman, Biochim. Biophys. Acta Mol. Cell Res. 1853, 1370 (2015)

    Article  Google Scholar 

  7. J.P. Klare, H.-J. Steinhoff, Photosynth. Res. 102, 377 (2009)

    Article  Google Scholar 

  8. C. Altenbach, S.L. Flitsch, H.G. Khorana, W.L. Hubbell, Biochemistry 28, 7806 (1989)

    Article  Google Scholar 

  9. J.P. Klare, Biol. Chem. 394, 1281 (2013)

    Article  Google Scholar 

  10. M.T. Ge, S.B. Rananavare, J.H. Freed, Biochim. Biophys. Acta 1036, 228 (1990)

    Article  Google Scholar 

  11. J.P. Gölz, S. Bockelmann, K. Mayer, H.J. Steinhoff, H. Wieczorek, M. Huss, J.P. Klare, D. Menche, ChemMedChem 11, 420 (2016)

    Article  Google Scholar 

  12. B. Joseph, A. Sikora, E. Bordignon, G. Jeschke, D.S. Cafiso, T.F. Prisner, Angew. Chemie Int. Ed. 54, 6196 (2015)

    Article  Google Scholar 

  13. M.M. Haugland, J.E. Lovett, E.A. Anderson, Chem. Soc. Rev. 47, 668 (2018)

    Article  Google Scholar 

  14. O. Krumkacheva, E. Bagryanskaya, Electron Paramagn. Reson. 25, 35 (2017)

    Article  Google Scholar 

  15. T.F. Cunningham, M.R. Putterman, A. Desai, W.S. Horne, S. Saxena, Angew. Chemie Int. Ed. 54, 6330 (2015)

    Article  Google Scholar 

  16. A. Feintuch, G. Otting, D. Goldfarb, Methods Enzymol. 563, 415 (2015)

    Article  Google Scholar 

  17. Z. Wu, A. Feintuch, A. Collauto, L.A. Adams, L. Aurelio, B. Graham, G. Otting, D. Goldfarb, J. Phys. Chem. Lett. 8, 5277 (2017)

    Article  Google Scholar 

  18. C. Gmeiner, D. Klose, E. Mileo, V. Belle, S.R.A. Marque, G. Dorn, F.H.T. Allain, B. Guigliarelli, G. Jeschke, M. Yulikov, J. Phys. Chem. Lett. 8, 4852 (2017)

    Article  Google Scholar 

  19. S. Van Doorslaer, eMagRes 6, 51 (2017). https://doi.org/10.1002/9780470034590.emrstm1517

    Article  Google Scholar 

  20. Y. Deligiannakis, M. Louloudi, N. Hadjiliadis, Coord. Chem. Rev. 204, 1 (2000)

    Article  Google Scholar 

  21. S. Van Doorslaer, E. Vinck, Phys. Chem. Chem. Phys. 9, 4620 (2007)

    Article  Google Scholar 

  22. S.A. Dzuba, D. Marsh, Electron Paramagn. Reson. 24, 102 (2015)

    Article  Google Scholar 

  23. J.A. Cieslak, P.J. Focia, A. Gross, Biochemistry 49, 1486 (2010)

    Article  Google Scholar 

  24. E.S. Salnikov, D.A. Erilov, A.D. Milov, Y.D. Tsvetkov, C. Peggion, F. Formaggio, C. Toniolo, J. Raap, S.A. Dzuba, Biophys. J. 91, 1532 (2006)

    Article  ADS  Google Scholar 

  25. R. Carmieli, N. Papo, H. Zimmermann, A. Potapov, Y. Shai, D. Goldfarb, Biophys. J. 90, 492 (2006)

    Article  ADS  Google Scholar 

  26. K.A. Åhrling, M.C.W. Evans, J.H.A. Nugent, R.J. Ball, R.J. Pace, Biochemistry 45, 7069 (2006)

    Article  Google Scholar 

  27. A. Volkov, C. Dockter, Y. Polyhach, H. Paulsen, G. Jeschke, J. Phys. Chem. Lett. 1, 663 (2010)

    Article  Google Scholar 

  28. L. Urban, H.-J. Steinhoff, Mol. Phys. 111, 2873 (2013)

    Article  ADS  Google Scholar 

  29. D.A. Erilov, R. Bartucci, R. Guzzi, A.A. Shubin, A.G. Maryasov, D. Marsh, S.A. Dzuba, L. Sportelli, J. Phys. Chem. B 109, 12003 (2005)

    Article  Google Scholar 

  30. A.D. Milov, R.I. Samoilova, A.A. Shubin, Y.A. Grishin, S.A. Dzuba, Appl. Magn. Reson. 35, 73 (2008)

    Article  Google Scholar 

  31. K.B. Konov, N.P. Isaev, S.A. Dzuba, Mol. Phys. 111, 2882 (2013)

    Article  ADS  Google Scholar 

  32. L. Bottorf, S. Rafferty, I.D. Sahu, R.M. McCarrick, G.A. Lorigan, J. Phys. Chem. B 121, 2961 (2017)

    Article  Google Scholar 

  33. G.F. Ames, K. Nikaido, I.X. Wang, P.Q. Liu, C.E. Liu, C. Hu, J. Bioenerg. Biomembr. 33, 79 (2001)

    Article  Google Scholar 

  34. J. Yu, J. Ge, J. Heuveling, E. Schneider, M. Yang, Proc. Natl. Acad. Sci. USA 112, 5243 (2015)

    Article  ADS  Google Scholar 

  35. M. Biasini, S. Bienert, A. Waterhouse, K. Arnold, G. Studer, T. Schmidt, F. Kiefer, T.G. Cassarino, M. Bertoni, L. Bordoli, T. Schwede, Nucleic Acids Res. 42, W252 (2014)

    Article  Google Scholar 

  36. G. Hagelueken, R. Ward, J.H. Naismith, O. Schiemann, Appl. Magn. Reson. 42, 377 (2012)

    Article  Google Scholar 

  37. N.R. Coordinators, Nucleic Acids Res. 45, D12 (2017)

    Article  Google Scholar 

  38. M. Sippach, D. Weidlich, D. Klose, C. Abé, J. Klare, E. Schneider, H.J. Steinhoff, Biochim. Biophys. Acta Biomembr. 1838, 1760 (2014)

    Article  Google Scholar 

  39. T. Eitinger, D.A. Rodionov, M. Grote, E. Schneider, F.E.M.S. Microbiol, Rev. 35, 3 (2011)

    Google Scholar 

  40. K.P. Locher, Nat. Struct. Mol. Biol. 23, 487 (2016)

    Article  Google Scholar 

  41. V. Eckey, D. Weidlich, H. Landmesser, U. Bergmann, E. Schneider, J. Bacteriol. 192, 2150 (2010)

    Article  Google Scholar 

  42. F. Sievers, A. Wilm, D. Dineen, T.J. Gibson, K. Karplus, W. Li, R. Lopez, H. McWilliam, M. Remmert, J. Soding, J.D. Thompson, D.G. Higgins, Mol. Syst. Biol. 7, 539 (2014)

    Article  Google Scholar 

  43. J. Heuveling, H. Landmesser, E. Schneider, J. Bacteriol. 201:e00521–18 (2019). https://doi.org/10.1128/jb.00521

    Google Scholar 

  44. A.V. Astashkin, S.A. Dikanov, Y.D. Tsvetkov, J. Struct. Chem. 25, 45 (1984)

    Article  Google Scholar 

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Acknowledgements

We thank Heidi Landmesser (Humboldt Universität zu Berlin) for excellent technical assistance. This work was supported by Alexander von Humboldt Foundation and DFG (STE640/10 to H.J.S. and SCHN274/16-1 to E.S.). Computational modeling was funded by the Russian Foundation for Basic Research grant 17-54-49004.

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Authors and Affiliations

  1. Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Novosibirsk, Russia

    Nikolay Isaev

  2. Fachbereich Physik, Universität Osnabrück, 49069, Osnabrück, Germany

    Nikolay Isaev & Heinz-Jürgen Steinhoff

  3. Institut für Biologie/Physiologie der Mikroorganismen, Humboldt Universität zu Berlin, 10115, Berlin, Germany

    Johanna Heuveling & Erwin Schneider

  4. The Federal Research Center Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia

    Nikita Ivanisenko

  5. Novosibirsk State University, Novosibirsk, Russia

    Nikita Ivanisenko

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  1. Nikolay Isaev
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  2. Johanna Heuveling
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  3. Nikita Ivanisenko
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  4. Erwin Schneider
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  5. Heinz-Jürgen Steinhoff
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Correspondence to Heinz-Jürgen Steinhoff.

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Isaev, N., Heuveling, J., Ivanisenko, N. et al. ESEEM Reveals Bound Substrate Histidine in the ABC Transporter HisQMP2. Appl Magn Reson 50, 883–893 (2019). https://doi.org/10.1007/s00723-019-01114-y

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  • DOI: https://doi.org/10.1007/s00723-019-01114-y

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