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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2004 Aug 29;359(1448):1277–1285. doi: 10.1098/rstb.2004.1504

Probing the role of water in protein conformation and function.

R P Rand 1
PMCID: PMC1693414  PMID: 15306382

Abstract

Life began in a bath of water and has never escaped it. Cellular function has forced the evolution of many mechanisms ensuring that cellular water concentration has never changed significantly. To free oneself of any conceptual distinction among all small molecules, solutes and solvents, means that experiments to probe water's specific role in molecular function can be designed like any classical chemical reaction. Such an 'osmotic stress' strategy will be described in general and for an enzyme, hexokinase. Water behaves like a reactant that competes with glucose in binding to hexokinase, and modulates its conformational change and activity. This 'osmotic stress' strategy, now applied to many very different systems, shows that water plays a significant role, energetically, in most macromolecular reactions. It can be required to fill obligatory space, it dominates nearest non-specific interactions between large surfaces, it can be a reactant modulating conformational change; all this in addition to its more commonly perceived static role as an integral part of stereospecific intramolecular structure.

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Selected References

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  1. Bennett W. S., Jr, Steitz T. A. Structure of a complex between yeast hexokinase A and glucose. II. Detailed comparisons of conformation and active site configuration with the native hexokinase B monomer and dimer. J Mol Biol. 1980 Jun 25;140(2):211–230. doi: 10.1016/0022-2836(80)90103-5. [DOI] [PubMed] [Google Scholar]
  2. Bezrukov S. M., Vodyanoy I., Parsegian V. A. Counting polymers moving through a single ion channel. Nature. 1994 Jul 28;370(6487):279–281. doi: 10.1038/370279a0. [DOI] [PubMed] [Google Scholar]
  3. Bezrukov S. M., Vodyanoy I. Probing alamethicin channels with water-soluble polymers. Effect on conductance of channel states. Biophys J. 1993 Jan;64(1):16–25. doi: 10.1016/S0006-3495(93)81336-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown M. P., Grillo A. O., Boyer M., Royer C. A. Probing the role of water in the tryptophan repressor-operator complex. Protein Sci. 1999 Jun;8(6):1276–1285. doi: 10.1110/ps.8.6.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Colombo M. F., Rau D. C., Parsegian V. A. Protein solvation in allosteric regulation: a water effect on hemoglobin. Science. 1992 May 1;256(5057):655–659. doi: 10.1126/science.1585178. [DOI] [PubMed] [Google Scholar]
  6. Dzingeleski G. D., Wolfenden R. Hypersensitivity of an enzyme reaction to solvent water. Biochemistry. 1993 Sep 7;32(35):9143–9147. doi: 10.1021/bi00086a020. [DOI] [PubMed] [Google Scholar]
  7. Kornblatt J. A., Hoa G. H. A nontraditional role for water in the cytochrome c oxidase reaction. Biochemistry. 1990 Oct 9;29(40):9370–9376. doi: 10.1021/bi00492a010. [DOI] [PubMed] [Google Scholar]
  8. Kornblatt J. A., Kornblatt M. J. Water as it applies to the function of enzymes. Int Rev Cytol. 2002;215:49–73. doi: 10.1016/s0074-7696(02)15005-4. [DOI] [PubMed] [Google Scholar]
  9. LeNeveu D. M., Rand R. P. Measurement and modification of forces between lecithin bilayers. Biophys J. 1977 May;18(2):209–230. doi: 10.1016/S0006-3495(77)85608-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leikin S., Parsegian V. A., Rau D. C., Rand R. P. Hydration forces. Annu Rev Phys Chem. 1993;44:369–395. doi: 10.1146/annurev.pc.44.100193.002101. [DOI] [PubMed] [Google Scholar]
  11. Leikin S., Rau D. C., Parsegian V. A. Direct measurement of forces between self-assembled proteins: temperature-dependent exponential forces between collagen triple helices. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):276–280. doi: 10.1073/pnas.91.1.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LiCata V. J., Allewell N. M. Measuring hydration changes of proteins in solution: applications of osmotic stress and structure-based calculations. Methods Enzymol. 1998;295:42–62. doi: 10.1016/s0076-6879(98)95034-0. [DOI] [PubMed] [Google Scholar]
  13. McIntosh T. J., Magid A. D., Simon S. A. Range of the solvation pressure between lipid membranes: dependence on the packing density of solvent molecules. Biochemistry. 1989 Sep 19;28(19):7904–7912. doi: 10.1021/bi00445a053. [DOI] [PubMed] [Google Scholar]
  14. Mitchell D. C., Litman B. J. Effect of protein hydration on receptor conformation: decreased levels of bound water promote metarhodopsin II formation. Biochemistry. 1999 Jun 15;38(24):7617–7623. doi: 10.1021/bi990634m. [DOI] [PubMed] [Google Scholar]
  15. Parsegian V. A., Fuller N., Rand R. P. Measured work of deformation and repulsion of lecithin bilayers. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2750–2754. doi: 10.1073/pnas.76.6.2750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Parsegian V. A., Rand R. P., Fuller N. L., Rau D. C. Osmotic stress for the direct measurement of intermolecular forces. Methods Enzymol. 1986;127:400–416. doi: 10.1016/0076-6879(86)27032-9. [DOI] [PubMed] [Google Scholar]
  17. Parsegian V. A., Rand R. P., Rau D. C. Macromolecules and water: probing with osmotic stress. Methods Enzymol. 1995;259:43–94. doi: 10.1016/0076-6879(95)59039-0. [DOI] [PubMed] [Google Scholar]
  18. Parsegian V. A., Rand R. P., Rau D. C. Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3987–3992. doi: 10.1073/pnas.97.8.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Racher K. I., Culham D. E., Wood J. M. Requirements for osmosensing and osmotic activation of transporter ProP from Escherichia coli. Biochemistry. 2001 Jun 19;40(24):7324–7333. doi: 10.1021/bi002331u. [DOI] [PubMed] [Google Scholar]
  20. Rand R. P., Fuller N. L., Butko P., Francis G., Nicholls P. Measured change in protein solvation with substrate binding and turnover. Biochemistry. 1993 Jun 15;32(23):5925–5929. doi: 10.1021/bi00074a001. [DOI] [PubMed] [Google Scholar]
  21. Rand R. P., Fuller N., Parsegian V. A., Rau D. C. Variation in hydration forces between neutral phospholipid bilayers: evidence for hydration attraction. Biochemistry. 1988 Oct 4;27(20):7711–7722. doi: 10.1021/bi00420a021. [DOI] [PubMed] [Google Scholar]
  22. Rand R. P., Parsegian V. A., Rau D. C. Intracellular osmotic action. Cell Mol Life Sci. 2000 Jul;57(7):1018–1032. doi: 10.1007/PL00000742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rau D. C., Lee B., Parsegian V. A. Measurement of the repulsive force between polyelectrolyte molecules in ionic solution: hydration forces between parallel DNA double helices. Proc Natl Acad Sci U S A. 1984 May;81(9):2621–2625. doi: 10.1073/pnas.81.9.2621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rau D. C., Parsegian V. A. Direct measurement of forces between linear polysaccharides xanthan and schizophyllan. Science. 1990 Sep 14;249(4974):1278–1281. doi: 10.1126/science.2144663. [DOI] [PubMed] [Google Scholar]
  25. Rau D. C., Parsegian V. A. Direct measurement of the intermolecular forces between counterion-condensed DNA double helices. Evidence for long range attractive hydration forces. Biophys J. 1992 Jan;61(1):246–259. doi: 10.1016/S0006-3495(92)81831-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rayner M. D., Starkus J. G., Ruben P. C., Alicata D. A. Voltage-sensitive and solvent-sensitive processes in ion channel gating. Kinetic effects of hyperosmolar media on activation and deactivation of sodium channels. Biophys J. 1992 Jan;61(1):96–108. doi: 10.1016/S0006-3495(92)81819-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reid C., Rand R. P. Probing protein hydration and conformational states in solution. Biophys J. 1997 Mar;72(3):1022–1030. doi: 10.1016/S0006-3495(97)78754-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Robinson C. R., Sligar S. G. Molecular recognition mediated by bound water. A mechanism for star activity of the restriction endonuclease EcoRI. J Mol Biol. 1993 Nov 20;234(2):302–306. doi: 10.1006/jmbi.1993.1586. [DOI] [PubMed] [Google Scholar]
  29. Rübenhagen R., Morbach S., Krämer R. The osmoreactive betaine carrier BetP from Corynebacterium glutamicum is a sensor for cytoplasmic K+. EMBO J. 2001 Oct 1;20(19):5412–5420. doi: 10.1093/emboj/20.19.5412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sidorova NYu, Rau D. C. The osmotic sensitivity of netropsin analogue binding to DNA. Biopolymers. 1995 Apr;35(4):377–384. doi: 10.1002/bip.360350405. [DOI] [PubMed] [Google Scholar]
  31. Simon S. A., McIntosh T. J. Magnitude of the solvation pressure depends on dipole potential. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9263–9267. doi: 10.1073/pnas.86.23.9263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Timasheff S. N. In disperse solution, "osmotic stress" is a restricted case of preferential interactions. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7363–7367. doi: 10.1073/pnas.95.13.7363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Timasheff S. N. The control of protein stability and association by weak interactions with water: how do solvents affect these processes? Annu Rev Biophys Biomol Struct. 1993;22:67–97. doi: 10.1146/annurev.bb.22.060193.000435. [DOI] [PubMed] [Google Scholar]
  34. Timasheff Serge N. Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components. Proc Natl Acad Sci U S A. 2002 Jul 3;99(15):9721–9726. doi: 10.1073/pnas.122225399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vodyanoy I., Bezrukov S. M., Parsegian V. A. Probing alamethicin channels with water-soluble polymers. Size-modulated osmotic action. Biophys J. 1993 Nov;65(5):2097–2105. doi: 10.1016/S0006-3495(93)81245-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wood J. M. Osmosensing by bacteria: signals and membrane-based sensors. Microbiol Mol Biol Rev. 1999 Mar;63(1):230–262. doi: 10.1128/mmbr.63.1.230-262.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zimmerberg J., Parsegian V. A. Polymer inaccessible volume changes during opening and closing of a voltage-dependent ionic channel. Nature. 1986 Sep 4;323(6083):36–39. doi: 10.1038/323036a0. [DOI] [PubMed] [Google Scholar]

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