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Interhelical hydrogen bonds in transmembrane region are important for function and stability of Ca2+-transporting ATPase

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Abstract

Ca2+-transporting adenosine triphosphatase (ATPase) of sarcoplasmic reticulum couples ATP hydrolysis with ion transport. Phosphorylation of the cytosolic region of the calcium-bound conformation (E1) of the protein leads to drastic conformational rearrangements of the transmembrane helices and the release of Ca2+. The resulting calcium-free conformation (E2) is less stable than the E1 form. The changes in van der Waals interactions and interhelical hydrogen bonding in the E1 and E2 conformations were compared. Conformational changes in the transmembrane region concomitant with the release of Ca2+ mainly affect the number of interhelical hydrogen bonds, which is reduced to half of that in E1 form, whereas the number of interhelical atomic pairwise contacts reflecting van der Waals interactions experience little change. The interhelical hydrogen bonds in Ca2+-transporting ATPase can be divided into two groups according to their roles: those that play a structural stabilizing role and those that are important for the correct geometry of the Ca2+ binding site. Interhelical hydrogen bonds in the transmembrane regions play important roles for the stability and specificity of helix-helix interactions in proteins where change of conformation is required for transport of ions or small molecules.

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References

  1. Toyoshima, C., Nakasako, M., and Nomura, O. H. (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution. Nature 405, 647–655.

    Article  PubMed  CAS  Google Scholar 

  2. Toyoshima, C., and Nomura, O. H. (2002) Structural changes in the calcium pump accompanying the dissociation of calcium. Nature 418, 605–611.

    Article  PubMed  CAS  Google Scholar 

  3. Perlin, D. S. (1998) Ion pumps as targets for therapeutic intervention: old and new paradigms. Electronic J. Biotech. 1, 55–64.

    Article  Google Scholar 

  4. MacLennan, D. H., Rice, W. J., and Green, N. M. (1997) The mechanism of Ca2+ transport by sarco(endo)plasmic reticulum Ca2+ ions-ATPases. J. Biol. Chem. 272, 28815–28818.

    Article  PubMed  CAS  Google Scholar 

  5. Lee, A. G., and East, J. M. (2001) What the structure of a calcium pump tells us about its mechanism. Biochem. J. 356, 665–683.

    Article  PubMed  CAS  Google Scholar 

  6. Eilers, M., Patel, A. B., Liu, W., and Smith, S. O. (2002) Comparison of helix interaction in membrane and soluble α-bundle proteins. Biophysical J. 82, 2720–2736.

    CAS  Google Scholar 

  7. Adamian, L., and Liang, J. (2001) Helix-helix packing and interfacial pairwise interactions of residues in membrane proteins. J. Mol. Biol. 311, 891–907.

    Article  PubMed  CAS  Google Scholar 

  8. MacKenzie, K. R., Prestegard, J. H., and Engelman, D. M. (1997) A transmembrane helix dimer: structure and implications. Science 276, 131–133.

    Article  PubMed  CAS  Google Scholar 

  9. Choma, C., Gratkowski, H., Lear, J. D., and DeGrado, W. F. (2000) Asparagine-mediated self-association of a model transmembrane helix. Nat. Structural Biol. 7, 161–166.

    Article  CAS  Google Scholar 

  10. Zhou, F. X., Cocco, M. J., Russ, W. P., Brunger, A. T., and Engelman, D. M. (2000) Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nat. Structural Biol. 7, 154–160.

    Article  CAS  Google Scholar 

  11. Adamian, L., and Liang, J. (2002) Interhelical hydrogen bonds and spatial motifs in membrane proteins: polar clamps and serine zippers. Proteins 47, 209–218.

    Article  PubMed  CAS  Google Scholar 

  12. Liang, J. (2002) Experimental and computational studies of determinants of membrane protein folding. Curr. Opin. Chem. Biol. 6, 878–884.

    Article  PubMed  CAS  Google Scholar 

  13. Adamian, L., Jackups, R., Binkowski, T. A., and Liang, J. (2003) Higher order interhelical spatial interactions in membrane proteins. J. Mol. Biol. in press.

  14. McDonald, I. K., and Thornton, J. M. (1994) Satisfying hydrogen bonding potential in proteins. J. Mol. Biol. 238, 777–793.

    Article  PubMed  CAS  Google Scholar 

  15. Edelsbrunner, H., and Mucke, E. P. (1994) 3-dimensional alpha-shapes. ACM Transactions Graphics 13, 43–72.

    Article  Google Scholar 

  16. Edelsbrunner, H., and Shah, N. R. (1996) Incremental topological flipping works for regular triangulations. Algorithmica 15, 223–241.

    Article  Google Scholar 

  17. Facello, M. A. (1995) Implementation of a randomized algorithm for Delaunay and regular triangulation in 3 dimensions. Comput. Aided Geom. D. 12, 349–370.

    Article  Google Scholar 

  18. Tsai, J., Taylor, R., Chothia, C., and Gerstein, M. (1999) The packing density in proteins: standard radii and volumes. J. Mol. Biol. 290, 253–266.

    Article  PubMed  CAS  Google Scholar 

  19. Berezovsky, I. N., Esipova, N., Tumanyan, V. G., and Namiot, V. A. (2000) A new approach for the calculation of the energy of van der Waals interaction in macromolecules of globular proteins. J. Biomolecular Structure Dynamics 17, 799–809.

    CAS  Google Scholar 

  20. Langosch, D., and Heringa, J. (1998) Interaction of transmembrane helices by a knobs-into-holes packing characteristic of soluble coiled coils. Proteins 31, 150–159.

    Article  PubMed  CAS  Google Scholar 

  21. Berezovsky, I. N., and Trifonov, E. N. (2001) Van der Waals locks: loop-n-lock structure of globular proteins. J. Mol. Biol. 307, 1419–1426.

    Article  PubMed  CAS  Google Scholar 

  22. Liang, J., Edelsbrunner, H., Fu, P., Sudhakar, P. V., and Subramaniam, S. (1998) Analytical shape computation of macromolecules: I. Molecular area and volume through alpha shape. Proteins 33, 1–17.

    Article  PubMed  CAS  Google Scholar 

  23. Liang, J., Edelsbrunner, H., Fu, P., Sudhakar, P. V., and Subramaniam, S. (1998) Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins. Proteins 33, 18–29.

    Article  PubMed  CAS  Google Scholar 

  24. Singh, J., and Thornton, J. M. (1992) Atlas of Protein Side-Chain Interactions. IRL Press, Oxford.

    Google Scholar 

  25. Rice, W. J., and MacLennan, D. H. (1996) Scanning mutagenesis reveals a similar pattern of mutation sensitivity in transmembrane sequences M4, M5, and M6, but not in M8, of the Ca2+-ATPase of sarcoplasmic reticulum (SERCA1a). J. Biol. Chem. 271, 31412–31419.

    Article  PubMed  CAS  Google Scholar 

  26. Clarke, D. M., Loo, T. W., and MacLennan, D. H. (1990) Functional consequences of alteration to polar amino acids located in the transmembrane domain of the Ca2+ ATPase of sarcoplasmic reticulum. J. Biol. Chem. 265, 6262–6267.

    PubMed  CAS  Google Scholar 

  27. Chen, L., Sumbilla, C., Lewis, D., et al. (1996) Short and long range functions of amino acids in the transmembrane region of the sarcoplasmic reticulum ATPase. J. Biol. Chem. 271, 10745–10752.

    Article  PubMed  CAS  Google Scholar 

  28. Adams, P., East, J. M., Lee, A. G., and O’Connor, C. D. (1998) Mutational analysis of transmembrane helices M3, M4, M5 and M7 of the fast-twitch Ca2+-ATPase. Biochem. J. 335, 131–138.

    PubMed  CAS  Google Scholar 

  29. Engelman, D. M., and Steitz, T. A. In: The Protein Folding Problem (Wetlaufer, D. B., ed.). westview, Boulder, Colorado, 1984, pp. 87–113.

    Google Scholar 

  30. Lemmon, M. A., Flanagan, J. M., Treutlein, H. R., Zhang, J., and Engelman, D. M. (1992) Sequence specificity in the dimerization of transmembrane α-helices. Biochemistry 31, 12719–12725.

    Article  PubMed  CAS  Google Scholar 

  31. Lemmon, M. A., Treutlein, H. R., Adams, P. D., Brunger, A. T., and Engelman, D. M. (1994) A dimerization motif for transmembrane α-helices. Nature Structural Biol. 1, 157–163.

    Article  CAS  Google Scholar 

  32. Fleming, K. G., and Engelman, D. M. (2001) Specificity in transmembrane helix-helix interactions can define a hierarchy of stability for sequence variants. Proc. Natl. Acad. Sci. USA. 98, 14340–14344.

    Article  PubMed  CAS  Google Scholar 

  33. Gratkowski, J., Lear, J. D., and DeGrado, W. F. (2001) Polar side chains drive the association of model transmembrane peptides. Proc. Natl. Acad. Sci. USA. 98, 880–885.

    Article  PubMed  CAS  Google Scholar 

  34. Dawson, J. P., Weinger, J. S., and Engelman, D. M. (2001) Motifs of serine and threonine can drive association of transmembrane helices. J. Mol. Biol. 316, 799–805.

    Article  CAS  Google Scholar 

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  1. Department of Bioengineering, University of Illinois at Chicago, 60607, IL

    Larisa Adamian & Jie Liang

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  1. Larisa Adamian
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  2. Jie Liang
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Correspondence to Jie Liang.

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Adamian, L., Liang, J. Interhelical hydrogen bonds in transmembrane region are important for function and stability of Ca2+-transporting ATPase. Cell Biochem Biophys 39, 1–12 (2003). https://doi.org/10.1385/CBB:39:1:1

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