Advertisement

The European Physical Journal Special Topics

, Volume 227, Issue 14, pp 1693–1704 | Cite as

Dynamics of the full-length yeast Hsp90 dimer

  • Florian Kandzia
  • Martin ZachariasEmail author
Regular Article
  • 16 Downloads
Part of the following topical collections:
  1. Particle Methods in Natural Science and Engineering

Abstract

The Hsp90 chaperone is a complex homodimeric biological assembly that assists in the folding of proteins. It can undergo global conformational changes between an open (Adenosindiphosphat, ADP-bound) and closed (Adenosintriphosphat, ATP-bound) state that are of functional importance. How the conformational transitions are triggered and coupled to chaperone function is not well understood. Molecular dynamics simulations in explicit solvent starting from either the closed conformation or the open conformation in different nucleotide bound states and in the apo (without nucleotide) state were performed. On the time scale of ~300 ns the simulations starting from the closed state stayed close to the starting conformation independent of the nucleotide bound state. In case of the open structure the simulations indicated large global fluctuations including movements towards a more closed state, however, no complete transitions to the closed state were observed. The analysis of conformational fluctuations indicates only modest differences in local fluctuations of the monomers for open vs. closed state and global dimer changes are mediated by small local motions of the C-terminal Hsp90 segments.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    B. Chen, W.H. Piel, L. Gui, E. Bruford, A. Monteiro, Genomics 86, 627 (2005)CrossRefGoogle Scholar
  2. 2.
    W.M. Obermann, H. Sondermann, A.A. Russo, N.P. Pavletich, F.U. Hartl, J. Cell Biol. 143, 901 (1998)CrossRefGoogle Scholar
  3. 3.
    B. Panaretou, C. Prodromou, S.M. Roe, R. O’Brien, J.E. Ladbury, P.W. Piper, L.H. Pearl, EMBO J. 17, 4829 (1998)CrossRefGoogle Scholar
  4. 4.
    R.E. Lackie, A. Maciejewski, V.G. Ostapchenko, J. Marques-Lopes, W.-Y. Choy, M.L. Duennwald, V.F. Prado, M.A.M. Prado, Front. Neurosci. 11, 254 (2017)CrossRefGoogle Scholar
  5. 5.
    L.B. Shelton, J. Koren, L.J. Blair, L.J. Blair, Front. Neurosci. 11, 724 (2017)CrossRefGoogle Scholar
  6. 6.
    K.A. Gallo, Chem. Biol. 13, 115 (2006)CrossRefGoogle Scholar
  7. 7.
    G.D. Lianos, G.A. Alexiou, A. Mangano, A. Mangano, S. Rausei, L. Boni, G. Dionigi, D.H. Roukos, Cancer Lett. 360, 114 (2015)CrossRefGoogle Scholar
  8. 8.
    K.A. Verba, R.Y.-R. Wang, A. Arakawa, Y. Liu, M. Shirouzu, S. Yokoyama, D.A. Agard, Science 352, 1542 (2016)ADSCrossRefGoogle Scholar
  9. 9.
    D.E. Dollins, J.J. Warren, R.M. Immormino, D.T. Gewirth, Mol. Cell 28, 41 (2007)CrossRefGoogle Scholar
  10. 10.
    A.K. Shiau, S.F. Harris, D.R. Southworth, D.A. Agard, Cell 127, 329 (2006)CrossRefGoogle Scholar
  11. 11.
    B. Hellenkamp, P. Wortmann, F. Kandzia, M. Zacharias, T. Hugel, Nat. Methods 14, 174 (2016)CrossRefGoogle Scholar
  12. 12.
    M.M.U. Ali, S.M. Roe, C.K. Vaughan, P. Meyer, B. Panaretou, P.W. Piper, C. Prodromou, L.H. Pearl, Nature 440, 1013 (2006)ADSCrossRefGoogle Scholar
  13. 13.
    G. Morra, R. Potestio, C. Micheletti, G. Colombo, PLoS Comput. Biol. 8, e1002433 (2012)ADSCrossRefGoogle Scholar
  14. 14.
    S. Sattin, J. Tao, G. Vettoretti, E. Moroni, M. Pennati, A. Lopergolo, L. Morelli, A. Bugatti, A. Zuehlke, M. Moses, T. Prince, T. Kijima, K. Beebe, M. Rusnati, L. Neckers, N. Zaffaroni, D.A. Agard, A. Bernardi, G. Colombo, Chem. Eur. J. 21, 13598 (2015)CrossRefGoogle Scholar
  15. 15.
    A. Rehn, E. Moroni, B.K. Zierer, F. Tippel, G. Morra, C. John, K. Richter, G. Colombo, J. Buchner, J. Mol. Biol. 428, 4559 (2016)CrossRefGoogle Scholar
  16. 16.
    J.A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K.E. Hauser, C. Simmerling, J. Chem. Theory Comput. 11, 3696 (2015)CrossRefGoogle Scholar
  17. 17.
    G. Morra, G. Verkhivker, G. Colombo, PLoS Comput. Biol. 5, e1000323 (2009)ADSCrossRefGoogle Scholar
  18. 18.
    K.A. Krukenberg, T.O. Street, L.A. Lavery, D.A. Agard, Q. Rev. Biophys. 44, 229 (2011)CrossRefGoogle Scholar

Copyright information

© EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Technical University of Munich, Physics Department T38GarchingGermany

Personalised recommendations