Skip to main content
SpringerLink
Log in

Molecular modeling of the tetramerization domain of human potassium channel Kv10.2 in different oligomeric states

  • Molecular Biology
  • Published:
Moscow University Biological Sciences Bulletin Aims and scope Submit manuscript

Abstract

A voltage-gated potassium channel Kv10.2 is expressed in the nervous system, but its functions and involvement in the development of human disease remain poorly understood. Mutant forms of the Kv10.2 channel were found in patients with epileptic encephalopathy and autism. Molecular modeling of the channel spatial structure is an important tool for gaining knowledge about the molecular aspects of the channel functioning and mechanisms responsible for pathogenesis. In the present work, molecular modeling of the helical fragment of the human Kv10.2 (hEAG2) C-terminal domain in dimeric, trimeric, and tetrameric forms was performed. The stability of all forms was confirmed by molecular dynamics simulation. Contacts and interactions, stabilizing the structure, were identified.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Saganich, M.J, Vega-Saenz de Miera, E., Nadal, M.S., Baker, H., Coetzee, W.A., and Rudy, B., Cloning of components of a novel subthreshold-activating K(+) channel with a unique pattern of expression in the cerebral cortex, J. Neurosci., 1999, vol. 19, no. 24, pp. 10789–10802.

    CAS  PubMed  Google Scholar 

  2. Asher, V., Sowter, H., Shaw, R., Bali, A., and Khan, R, Eag and HERG potassium channels as novel therapeutic targets in cancer, World J. Surg. Oncol., 2010, vol. 8, no. 1, p.113.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Yang, Y., Vasylyev, D.V., Dib-Hajj, F., Veeramah, K.R., Hammer, M.F., Dib-Hajj, S.D., and Waxman, S.G., Multistate structural modeling and voltageclamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state, J. Neurosci., 2013, vol. 33, no. 42, pp. 16586–16593.

    Article  CAS  PubMed  Google Scholar 

  4. Wulff, H., Pardo, L.A., and Castle, N.A, Voltagegated potassium channels as therapeutic targets, Nat. Rev. Drug Discov., 2009, vol. 8, no. 12, pp. 982–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ju, M. and Wray, D, Molecular identification and characterisation of the human eag2 potassium channel, FEBS Lett., 2002, vol. 524, nos 1-3, pp. 204–210.

    Article  CAS  PubMed  Google Scholar 

  6. Schönherr, R., Gessner, G., Löber, K., and Heinemann, S.H., Functional distinction of human EAG1 and EAG2 potassium channels, FEBS Lett., 2002, vol. 514, nos. 2–3, pp. 204–208.

    Article  PubMed  Google Scholar 

  7. Karlova, M.G., Pischalnikova, A.V., Ramonova, A.A., Moisenovich, M.M., Sokolova, O.S., and Shaitan, K.V, In vitro fluorescence assay to study the folding of Kv ion channels, Biophysics, 2011, vol. 56, no. 2, pp. 243–249.

    Article  Google Scholar 

  8. Ludwig, J., Owen, D., and Pongs, O., Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-à-go-go potassium channel, EMBO J., 1997, vol. 16, no. 21, pp. 6337–6345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jenke, M., Sánchez, A., Monje, F., Stühmer, W., Weseloh, R.M., and Pardo, L.A., C-terminal domains implicated in the functional surface expression of potassium channels, EMBO J., 2003, vol. 22, no. 3, pp. 395–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wiener, R., Haitin, Y., Shamgar, L., Fernández-Alonso, M.C., Martos, A., Chomsky-Hecht, O., Rivas, G., Attali, B., and Hirsch, J.A, The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction, J. Biol. Chem., 2008, vol. 283, no. 9, pp. 5815–5830.

    Article  CAS  PubMed  Google Scholar 

  11. Ju, M. and Wray, D, Molecular regions responsible for differences in activation between hEAG channels, Bio-chem. Biophys. Res. Commun., 2006, vol. 342, no. 4, pp. 1088–1097.

    Article  CAS  Google Scholar 

  12. Stevens, L., Ju, M., and Wray, D, Roles of surface residues of intracellular domains of heag potassium channels, Eur. Biophys. J., 2009, vol. 38, no. 4, pp. 523–532.

    Article  CAS  PubMed  Google Scholar 

  13. Sokolova, O.S., Shaitan, K.V., Grizel, A.V., Popinako, A.V., Karlova, M.G., and Kirpichnikov, M.P, Threedimensional structure of human voltage-gated ion channel Kv10.2 studied by electron microscopy of macromolecules and molecular modeling, Russ. J. Bioorganic Chem., 2012, vol. 38, no. 2, pp. 152–158.

    Article  CAS  Google Scholar 

  14. Whicher, J.R. and Mackinnon, R, Structure of the voltage-gated K+ channel Eag1 reveals an alternative voltage sensing mechanism, Science, 2016, vol. 353, no. 6300, pp. 664–669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Novoseletsky, V.N., Volyntseva, A.D., Shaitan, K.V., Kirpichnikov, M.P., and Feofanov, A.V, Modeling of the binding of peptide blockers to voltage-gated potassium channels: Approaches and evidence, Acta Naturae, 2016, vol. 8, no. 2, pp. 35–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Glukhov, G.S., Popinako, A.V., Grizel, A.V., Shaitan, K.V., and Sokolova, O.S, The structure of a human voltage-gated potassium Kv10.2 channel which lacks a cytoplasmic pas domain, Biophysics, 2016, vol. 61, no. 4, pp. 591–595.

    Article  CAS  Google Scholar 

  17. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., and Berendsen, H.J.C., GROMACS: Fast, flexible, and free, J. Comput. Chem., 2005, vol. 26, no. 16, pp. 1701–1718.

    Article  Google Scholar 

  18. Strelkov, S.V. and Burkhard, P, Analysis of a-helical coiled coils with the program TWISTER reveals a structural mechanism for stutter compensation, J. Struct. Biol., 2002, vol. 137, nos. 1–2, pp. 54–64.

    Article  CAS  PubMed  Google Scholar 

  19. Baker, N.A., Sept, D., Joseph, S., Holst, M.J., and McCammon, J.A, Electrostatics of nanosystems: Application to microtubules and the ribosome, Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, no. 18, pp. 10037–10041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schymkowitz, J., Borg, J., Stricher, F., Nys, R., Rousseau, F., and Serrano, L, The FoldX web server: An online force field, Nucleic Acid Res., 2005, vol. 33, suppl. 2, pp. W382–W388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vincent, T.L., Green, P.J., and Woolfson, D.N., LOGICOIL–multi-state prediction of coiled-coil oligomeric state, Bioinformatics, 2013, vol. 29, no. 1, pp. 69–76.

    Article  CAS  PubMed  Google Scholar 

  22. Rao, J.N., Rivera-Santiago, R., Li, X.E., Lehman, W., and Dominguez, R., Structural analysis of smooth muscle tropomyosin a and ß isoforms, J. Biol. Chem., 2012, vol. 287, no. 5, pp. 3165–3174.

    Article  CAS  PubMed  Google Scholar 

  23. Xu, Q. and Minor, D.L, Crystal structure of a trimeric form of the K(V)7.1 (KCNQ1) A-domain tail coiledcoil reveals structural plasticity and context dependent changes in a putative coiled-coil trimerization motif, Protein Sci., 2009, vol. 18, no. 10, pp. 2100–2114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kammerer, R., Kostrewa, D., Progias, P., Honnappa, S., Avila, D., Lustig, A., Winkler, F.K., Pieters, J., and Steinmetz, M.O., A conserved trimerization motif controls the topology of short coiled coils, Proc. Natl. Acad. Sci. U.S.A., 2005, vol. 102, no. 39, pp. 13891–13896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Howard, R.J., Clark, K.A., Holton, J.M., and Minor, D.L, Structural insight into KCNQ (Kv7) channel assembly and channelopathy, Neuron, 2007, vol. 53, no. 5, pp. 663–675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sadovnichy, V., Tikhonravov, A., Voevodin, V., and Opanasenko, V, Supercomputing at Moscow State University, in Contemporary High Performance Computing: From Petascale toward Exascale, Vetter, J.S., Ed., Boca Raton, FL: Chapman & Hall/CRC, 2013, pp. 283–307.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, Moscow State University, Moscow, 119234, Russia

    V. N. Novoseletsky, A. D. Volyntseva, K. V. Shaitan & O. S. Sokolova

Authors
  1. V. N. Novoseletsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. D. Volyntseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. V. Shaitan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. S. Sokolova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. N. Novoseletsky.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novoseletsky, V.N., Volyntseva, A.D., Shaitan, K.V. et al. Molecular modeling of the tetramerization domain of human potassium channel Kv10.2 in different oligomeric states. Moscow Univ. Biol.Sci. Bull. 72, 69–73 (2017). https://doi.org/10.3103/S0096392517020031

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0096392517020031

Keywords

Search

Navigation