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Volume and Compressibility of Proteins

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High Pressure Bioscience

Part of the book series: Subcellular Biochemistry ((SCBI,volume 72))

Abstract

The partial specific (or molar) volume, expansibility, and compressibility of a protein are fundamental thermodynamic quantities for characterizing its structure in solution. We review the definitions, measurements, and implications of these volumetric quantities in relation to protein structural biology. The partial specific volumes under constant molality (isomolal) and chemical potential (isopotential) conditions of the cosolvent (multicomponent systems) are explained in terms of preferential solvent interactions relevant to the solubility and stability of proteins. The partial expansibility is briefly discussed in terms of the effects of temperature on protein–solvent interactions (hydration) and internal packing defects (cavities). We discuss the compressibility–structure–function relationships of proteins based on analyses of the correlations between the partial adiabatic compressibilities and the structures or functions of various globular proteins (including mutants), focusing on the roles of the internal cavities in structural fluctuations. The volume and compressibility changes associated with various conformational transitions are also discussed in terms of the changes in hydration and cavities in order to elucidate the nonnative structures and the transition mechanisms, especially those associated with pressure denaturation.

An erratum to this chapter is available at http://dx.doi.org/10.1007/978-94-017-9918-8_34

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References

  • Akasaka K (2006) Probing conformational fluctuation of proteins by pressure perturbation. Chem Rev 106:1814–1835

    Article  CAS  PubMed  Google Scholar 

  • Akasaka K, Latif AR, Nakamura A, Matsuo K, Tachibana H, Gekko K (2007) Amyloid protofibril is highly voluminous and compressible. Biochemistry 46:10444–10450

    Article  CAS  PubMed  Google Scholar 

  • Arakawa T, Timasheff SN (1982) Preferential interactions of proteins with salts in concentrated solutions. Biochemistry 21:6545–6552

    Article  CAS  PubMed  Google Scholar 

  • Arakawa T, Timasheff SN (1984) Protein stabilization and destabilization by guanidinium salts. Biochemistry 23:5924–5929

    Article  CAS  PubMed  Google Scholar 

  • Blandamer MJ, Davis MI, Douhéret G, Reis JCR (2001) Apparent molar isentropic compressions and expansions of solutions. Chem Soc Rev 30:8–15

    Article  CAS  Google Scholar 

  • Brandts JF, Oliveira RJ, Westort C (1970) Thermodynamics of protein denaturation: effect of pressure on the denaturation of ribonuclease A. Biochemistry 9:1038–1047

    Article  CAS  PubMed  Google Scholar 

  • Casassa EF, Eisenberg H (1964) Thermodynamic analysis of multicomponent solutions. Adv Protein Chem 19:287–395

    Article  CAS  PubMed  Google Scholar 

  • Chalikian TV (2003) Volumetric properties of proteins. Annu Rev Biophys Biomol Struct 32:207–235

    Article  CAS  PubMed  Google Scholar 

  • Chalikian TV, Gindikin VS, Breslauer KJ (1995) Volumetric characterizations of the native, molten globule and unfolded states of cytochrome c at acidic pH. J Mol Biol 250:291–306

    Article  CAS  PubMed  Google Scholar 

  • Chalikian TV, Totrov M, Abagyan R, Breslauer KJ (1996) The hydration of globular proteins as derived from the volume and compressibility measurements: cross correlating thermodynamic and structural data. J Mol Biol 260:588–603

    Article  CAS  PubMed  Google Scholar 

  • Chalikain TV, Völker J, Anafi D, Breslauer KJ (1997) The native and the heat-induced denatured states of α-chymotrypsinogen A: thermodynamic and spectroscopic studies. J Mol Biol 274:237–252

    Article  Google Scholar 

  • Cohn EJ, Edsall JT (1943) Density and apparent specific volume of proteins. In: Cohn EJ, Edsall JT (eds) Proteins, amino acids and peptides. Reinhold, New York, pp 370–381

    Google Scholar 

  • Cooper A (1976) Thermodynamic fluctuations in protein molecules. Proc Natl Acad Sci U S A 73:2740–2741

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dadarlat VM, Post CB (2001) Insights into protein compressibility from molecular dynamics simulations. J Phys Chem B 105:715–724

    Article  CAS  Google Scholar 

  • Dubins DN, Filfil R, Macgregor RB Jr, Chalikian TV (2000) Role of water in protein–ligand interactions: volumetric characterization of the binding of 2’-CMP and 3’-CMP to ribonuclease A. J Phys Chem B 104:390–401

    Article  CAS  Google Scholar 

  • Dubins DN, Filfil R, Macgregor RB Jr, Chalikian TV (2003) Volume and compressibility changes accompanying thermally-induced native-to-unfolded and molten globule-to-unfolded transitions of cytochrome c: a high pressure study. Biochemistry 42:8671–8678

    Article  CAS  PubMed  Google Scholar 

  • Durchschlag H (1986) Specific volumes of biological macromolecules and some other molecules of biological interest. In: Hinz HJ (ed) Thermodynamic data for biochemistry and biotechnology. Springer, Berlin, pp 45–128

    Chapter  Google Scholar 

  • Fasman GD (ed) (1976) Handbook of biochemistry and molecular biology, vol 2, 3rd edn. CRC Press, Cleveland

    Google Scholar 

  • Filfil R, Chalikian TV (2000) Volume and spectroscopic characterizations of the native and acid-induced denatured states of staphylococcal nuclease. J Mol Biol 299:827–842

    Article  CAS  PubMed  Google Scholar 

  • Fourme R, Kahn R, Mezouar M, Girard E, Hoerentrup C, Prangé T, Ascone I (2001) High-pressure protein crystallography (HPPX): instrumentation, methodology and results on lysozyme crystals. J Synchrotron Radiat 8:1149–1156

    Article  CAS  PubMed  Google Scholar 

  • Fourme R, Girard E, Akasaka K (2012) High-pressure macromolecular crystallography and NMR: status, achievements and prospects. Curr Opin Struct Biol 22:636–642

    Article  CAS  PubMed  Google Scholar 

  • Frauenfelder H, Hartmann H, Karplus M, Kuntz ID Jr, Kuriyan J, Parak F, Petsko GA, Ringe D, Titon RF Jr, Connolly ML, Max N (1987) Thermal expansion of a protein. Biochemistry 26:254–261

    Article  CAS  PubMed  Google Scholar 

  • Gavish B, Gratton E, Hardy CJ (1983) Adiabatic compressibility of globular proteins. Proc Natl Acad Sci U S A 80:750–754

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gekko K (1991) Flexibility of globular proteins in water as revealed by compressibility. In: Levine H, Slade L (eds) Water relationship in food. Plenum Press, New York, pp 753–771

    Chapter  Google Scholar 

  • Gekko K (2002) Compressibility gives new insight into protein dynamics and enzyme function. Biochim Biophys Acta 1595:382–386

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Hasegawa Y (1986) Compressibility-structure relationship of globular proteins. Biochemistry 25:6563–6571

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Hasegawa Y (1989) Effect of temperature on the compressibility of native globular proteins. J Phys Chem 93:426–429

    Article  CAS  Google Scholar 

  • Gekko K, Koga S (1984) The stability of protein structure in aqueous propylene glycol: amino acid solubility and preferential solvation of protein. Biochim Biophys Acta 786:151–160

    Article  CAS  Google Scholar 

  • Gekko K, Morikawa T (1981) Preferential hydration of bovine serum albumin in polyhydric alcohol-water mixtures. J Biochem 90:39–50

    CAS  PubMed  Google Scholar 

  • Gekko K, Noguchi H (1979) Compressibility of globular proteins in water at 25 °C. J Phys Chem 83:2706–2714

    Article  CAS  Google Scholar 

  • Gekko K, Timasheff SN (1981) Mechanism of protein stabilization by glycerol: preferential hydration in glycerol-water mixtures. Biochemistry 20:4667–4676

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Yamagami K (1991) Flexibility of food proteins as revealed by compressibility. J Agric Food Chem 39:57–62

    Article  CAS  Google Scholar 

  • Gekko K, Yamagami K (1998) Compressibility and volume changes of lysozyme due to inhibitor binding. Chem Lett 27:839–840

    Article  Google Scholar 

  • Gekko K, Kunori Y, Takeuchi H, Ichihara S, Kodama M (1994) Point mutations at glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function. J Biochem 116:34–41

    CAS  PubMed  Google Scholar 

  • Gekko K, Tamura Y, Ohmae E, Hayashi H, Kagamiyama H, Ueno H (1996) A large compressibility change of protein induced by a single amino acid substitution. Protein Sci 5:542–545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gekko K, Kamiyama T, Ohmae E, Katayanagi K (2000) Single amino acid substitutions in flexible loops can induce large compressibility changes in dihydrofolate reductase. J Biochem 128:21–27

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Kimoto A, Kamiyama T (2003) Effects of disulfide bonds on compactness of protein molecules revealed by volume, compressibility, and expansibility changes during reduction. Biochemistry 42:13746–13753

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Obu M, Li J, Lee JC (2004) A linear correlation between the energetics of allosteric communication and protein flexibility in the Escherichia coli cyclic AMP receptor protein revealed by mutation-induced changes in compressibility and amide hydrogen-deuterium exchange. Biochemistry 43:3844–3852

    Article  CAS  PubMed  Google Scholar 

  • Gekko K, Araga M, Kamiyama T, Ohmae E, Akasaka K (2009) Pressure dependence of the apparent specific volume of bovine serum albumin: insight into the difference between isothermal and adiabatic compressibilities. Biophys Chem 144:67–71

    Article  CAS  PubMed  Google Scholar 

  • Greenspan MG, Tschiegg CE (1956) Sing-around ultrasonic velocimeter for liquids. Rev Sci Instrum 28:897–901

    Article  Google Scholar 

  • Hattori M, Li H, Yamada H, Akasaka K, Hengstenberg W, Gronwald W, Kalbitzer HR (2004) Infrequent cavity-forming fluctuations in HPr from Staphylococcus carnosus revealed by pressure- and temperature-dependent tyrosine ring flips. Protein Sci 13:3104–3114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hawley SA (1971) Reversible pressure–temperature denaturation of chymotrypsinogen. Biochemistry 10:2436–2442

    Article  CAS  PubMed  Google Scholar 

  • Hinz HJ (ed) (1986) Thermodynamic data for biochemistry and biotechnology. Springer, Berlin

    Google Scholar 

  • Imai T, Kovalenko A, Hirata F (2005) Partial molar volume of proteins studied by the three-dimensional reference interaction site model theory. J Phys Chem B 109:6658–6665

    Article  CAS  PubMed  Google Scholar 

  • Imai T, Ohyama S, Kovalenko A, Hirata F (2007) Theoretical study of the partial molar volume change associated with the pressure-induced structural transition of ubiquitin. Protein Sci 16:1927–1933

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iwakura M, Maki K, Takahashi H, Takenawa T, Yokota A, Katayanagi K, Kamiyama T, Gekko K (2006) Evolutional design of a hyperactive cysteine- and methionine-free mutant of Escherichia coli dihydrofolate reductase. J Biol Chem 281:13234–13246

    Article  CAS  PubMed  Google Scholar 

  • Kamiyama T, Gekko K (1997) Compressibility and volume changes of lysozyme due to guanidine hydrochloride denaturation. Chem Lett 26:1063–1064

    Article  Google Scholar 

  • Kamiyama T, Gekko K (2000) Effects of ligand binding on the flexibility of dihydrofolate reductase as revealed by compressibility. Biochim Biophys Acta 1478:257–266

    Article  CAS  PubMed  Google Scholar 

  • Kamiyama T, Sadahide Y, Nogusa Y, Gekko K (1999) Polyol-induced molten globule of cytochrome c: an evidence for stabilization by hydrophobic interaction. Biochim Biophys Acta 1434:44–57

    Article  CAS  PubMed  Google Scholar 

  • Karplus M, McCammon JA (1981) The internal dynamics of globular proteins. CRC Crit Rev Biochem 9:293–349

    Article  CAS  PubMed  Google Scholar 

  • Kauzmann W (1959) Some factors in the interpretation of protein denaturation. Adv Protein Chem 14:1–63

    Article  CAS  PubMed  Google Scholar 

  • Kharakoz DP (2000) Protein compressibility, dynamics, and pressure. Biophys J 79:511–525

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kharakoz DP, Sarvazyan AP (1993) Hydration and intrinsic compressibilities of globular proteins. Biopolymers 33:11–26

    Article  CAS  PubMed  Google Scholar 

  • Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • Kitahara R, Sareth S, Yamada H, Ohmae E, Gekko K, Akasaka K (2000) High pressure NMR reveals active-site hinge motion of folate-bound Escherichia coli dihydrofolate reductase. Biochemistry 39:12789–12795

    Article  CAS  PubMed  Google Scholar 

  • Kratky O, Leopold H, Stabinger H (1973) The determination of the partial specific volume of proteins by the mechanical oscillator technique. Methods Enzymol 27:98–110

    Article  CAS  PubMed  Google Scholar 

  • Kundrot CM, Richards FM (1987) Crystal structure of hen egg-white lysozyme at a hydrostatic pressure of 1000 atmospheres. J Mol Biol 193:157–170

    Article  CAS  PubMed  Google Scholar 

  • Kupke DW (1973) Density and volume change measurements. In: Leach SJ (ed) Physical principles and techniques of protein chemistry. Academic, New York, pp 1–75, part C

    Google Scholar 

  • Lassalle MW, Yamada H, Akasaka K (2000) The pressure-temperature free energy-landscape of staphylococcal nuclease monitored by (1)H NMR. J Mol Biol 298:293–302

    Article  CAS  PubMed  Google Scholar 

  • Lee BK, Richards FM (1971) The interpretation of protein structures: estimation of static accessibility. J Mol Biol 55:379–400

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Timasheff SN (1974) Partial specific volumes and interactions with solvent components of proteins in guanidine hydrochloride. Biochemistry 13:257–265

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Timasheff SN (1981) The stabilization of proteins by sucrose. J Biol Chem 256:7193–7201

    CAS  PubMed  Google Scholar 

  • Lee JC, Gekko K, Timasheff SN (1979) Measurements of preferential solvent interactions by densimetric techniques. Methods Enzymol 61:26–49

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Tikhomirova A, Shalvardjian N, Chalikian TV (2008) Partial molar volumes and adiabatic compressibilities of unfolded protein states. Biophys Chem 134:185–199

    Article  CAS  PubMed  Google Scholar 

  • Lumry R, Rosenberg A (1975) The mobile defect hypothesis of protein function. Coll Int CNRS L’Eau Syst Biol 246:55–63

    Google Scholar 

  • Masterton WL, Seiler HK (1968) Apparent and partial molal volumes of water in organic solvents. J Phys Chem 72:4257–4262

    Article  CAS  Google Scholar 

  • Millero FJ, Ward GK, Chetirkin P (1976) Partial specific volume, expansibility, compressibility, and heat capacity of aqueous lysozyme solutions. J Biol Chem 251:4001–4004

    CAS  PubMed  Google Scholar 

  • Mimura S, Yamato T, Kamiyama T, Gekko K (2012) Nonneutral evolution of volume fluctuations in lysozymes revealed by normal-mode analysis of compressibility. Biophys Chem 161:39–45

    Article  CAS  PubMed  Google Scholar 

  • Mori K, Seki Y, Yamada Y, Matsumoto H, Soda K (2006) Evaluation of intrinsic compressibility of proteins by molecular dynamics simulation. J Chem Phys 125:054903

    Article  PubMed  Google Scholar 

  • Na GC, Timasheff SN (1981) Interaction of calf brain tubulin with glycerol. J Mol Biol 151:165–178

    Article  CAS  PubMed  Google Scholar 

  • Nölting B (1995) Relation between adiabatic and pseudoadiabatic compressibility in ultrasonic velocimetry. J Theor Biol 175:191–196

    Article  PubMed  Google Scholar 

  • Nölting B, Sligar SG (1993) Adiabatic compressibility of molten globules. Biochemistry 32:12319–12323

    Article  PubMed  Google Scholar 

  • Ohmae E, Iriyama K, Ichihara S, Gekko K (1996) Effects of point mutation at a flexible loop glycine-67 of Escherichia coli dihydrofolate reductase on its stability and function. J Biochem 119:703–710

    Article  CAS  PubMed  Google Scholar 

  • Ohmae E, Ishimura K, Iwakura M, Gekko K (1998) Effects of point mutation at a flexible loop alanine-145 of Escherichia coli dihydrofolate reductase on its stability and function. J Biochem 123:839–846

    Article  CAS  PubMed  Google Scholar 

  • Paci E, Marchi M (1996) Intrinsic compressibility and volume compression in solvated proteins by molecular dynamic simulation at high pressure. Proc Natl Acad Sci U S A 93:11609–11614

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pain RH (1987) Protein structure. New light on old defects. Nature 326:247

    Article  CAS  PubMed  Google Scholar 

  • Pinfield VJ, Povey MJW (1997) Thermal scattering must be accounted for in the determination of adiabatic compressibility. J Phys Chem B 101:1110–1112

    Article  CAS  Google Scholar 

  • Prehoda KE, Mooberry ES, Markley JL (1998) Pressure denaturation of proteins: evaluation of compressibility effects. Biochemistry 37:5785–5790

    Article  CAS  PubMed  Google Scholar 

  • Reiss H (1965) Scaled particle methods in the statistical thermodynamics of fluids. Adv Chem Phys 9:1–84

    Google Scholar 

  • Richards FM (1977) Area, volumes, packing and protein structure. Annu Rev Biophys Bioeng 6:151–176

    Article  CAS  PubMed  Google Scholar 

  • Sarvazyan AP (1991) Ultrasonic velocity of biological compounds. Annu Rev Biophys Biophys Chem 20:321–342

    Article  CAS  PubMed  Google Scholar 

  • Sarvazyan AP, Kharakoz DP (1977) Acoustical studies of the conformation states of proteins in aqueous solutions. In: Frank GM (ed) Molecular and cell biophysics. Nauka, Moscow, pp 93–106

    Google Scholar 

  • Schweiker KL, Makhatadze GI (2009) Use of pressure perturbation calorimetry to characterize the volumetric properties of proteins. Methods Enzymol 466:527–547

    Article  CAS  PubMed  Google Scholar 

  • Seemann H, Winter R, Royer CA (2001) Volume, expansivity and isothermal compressibility changes associated with temperature and pressure unfolding of Staphylococcal nuclease. J Mol Biol 307:1091–1102

    Article  CAS  PubMed  Google Scholar 

  • Smeller L (2002) Pressure-temperature phase diagrams of biomolecules. Biochim Biophys Acta 1595:11–29

    Article  CAS  PubMed  Google Scholar 

  • Smolin N, Winter R (2006) A molecular dynamics simulation of SNase and its hydration shell at high temperature and high pressure. Biochim Biophys Acta 1764:522–534

    Article  CAS  PubMed  Google Scholar 

  • Son I, Shek YS, Dubins DN, Chalikian TV (2012) Volumetric characterization of tri-N-acetylglucosamine binding to lysozyme. Biochemistry 51:5784–5790

    Article  CAS  PubMed  Google Scholar 

  • Tamura Y, Gekko K (1995) Compactness of thermally and chemically denatured ribonuclease A as revealed by volume and compressibility. Biochemistry 34:1878–1884

    Article  CAS  PubMed  Google Scholar 

  • Tamura Y, Gekko K, Yoshioka K, Vonderviszt F, Namba K (1997) Adiabatic compressibility of flagellin and flagellar filament of Salmonella typhimurium. Biochim Biophys Acta 1335:120–126

    Article  CAS  PubMed  Google Scholar 

  • Taulier N, Chalikian TV (2001) Characterization of pH-induced transitions of β-lactoglobulin: ultrasonic, densimetric, and spectroscopic studies. J Mol Biol 314:873–889

    Article  CAS  PubMed  Google Scholar 

  • Taulier N, Chalikian TV (2002) Compressibility of protein transitions. Biophim Biophys Acta 1595:48–70

    Article  CAS  Google Scholar 

  • Tilton RF Jr, Dewan JC, Petsko GA (1992) Effects of temperature on protein structure and dynamics: X-ray crystallographic studies of the protein ribonuclease-A at nine different temperatures from 98 to 320 K. Biochemistry 31:2469–2481

    Article  CAS  PubMed  Google Scholar 

  • Timasheff SN (1995) Preferential interactions of water and cosolvents with proteins. In: Gregory RB (ed) Protein-solvent interactions. Marcel Dekker, New York, pp 445–482

    Google Scholar 

  • Woodward CK, Carulla N, Barany G (2004) Native state hydrogen-exchange analysis of protein folding and protein motional domains. Methods Enzymol 380:379–400

    Article  CAS  PubMed  Google Scholar 

  • Wyman J, Gill J (eds) (1990) Binding and linkage: functional chemistry of biological macromolecules. University Science, Mill Valley

    Google Scholar 

  • Yamato T, Higo J, Seno Y, Go N (1993) Conformational deformation in deoxymyoglobin by hydrostatic pressure. Proteins 16:327–340

    Article  CAS  PubMed  Google Scholar 

  • Zamyatnin AA (1984) Amino acid, peptide, and protein volume in solution. Annu Rev Biophys Bioeng 13:145–165

    Article  CAS  PubMed  Google Scholar 

  • Zhai Y, Okoro L, Cooper A, Winter R (2011) Applications of pressure perturbation calorimetry in biophysical studies. Biophys Chem 156:13–23

    Article  CAS  PubMed  Google Scholar 

  • Zipp A, Kauzmann W (1973) Pressure denaturation of metmyoglobin. Biochemistry 12:4217–4228

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

We thank Dr. Tadashi Kamiyama of Kinki University for his helpful comments and careful reading of the manuscript.

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Gekko, K. (2015). Volume and Compressibility of Proteins. In: Akasaka, K., Matsuki, H. (eds) High Pressure Bioscience. Subcellular Biochemistry, vol 72. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9918-8_5

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