Advertisement

The Aqueous Interface of a Soluble Protein or the Birth of Epistructural Biology

  • Ariel Fernández Stigliano
Chapter

Abstract

For several decades we have witnessed the meteoric development of structural biology. The unraveling of molecular shapes is substantively advancing our understanding of cellular processes. After the pioneering forays in structural biology, we have also seen a veritable deluge of research publications in the related field of molecular biophysics. But this field did not enjoy quite the same level of success as its parental discipline. Despite much effort, the core problems in molecular biophysics continue to challenge researchers. In spite of enticing promises, it is felt that we are nowhere near cracking the protein folding problem from first principles, that we are far from unraveling the physicochemical basis of enzyme catalysis and protein associations, and that we are still unable to engineer therapeutic drugs based on our current understanding of molecular interactions. The acknowledgment of how exquisitely the structure of proteins and their aqueous environment are dynamically entangled attests to the overdue recognition that the biomolecular phenomena cannot be effectively understood without dealing with interfacial behavior. There is an urge to grasp how biological behavior is mediated and affected by the structuring of biomolecular interfaces, in turn determined—somehow—by the structure of proteins. This chapter squarely addresses this imperative and serves as an introduction to a new discipline that we have named epistructural biology. The field may be broadly described as the physicochemical study of the interplay between water and biomolecular structure across the interface. As shown in this chapter, a concept of paramount importance for epistructural biology is the dehydron, a special type of structural defect in soluble proteins recognized as causative of interfacial tension. The role of dehydrons as determinants of the structural and dynamic organization of the aqueous interface will be delineated and the implications for the understanding and control of biomolecular events will be highlighted.

Keywords

Soluble Protein Disulfide Bond Interfacial Tension Intramolecular Hydrogen Bond Solvation Shell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Wernet P, Nordlund D, Bergmann U, Cavalleri M, Odelius M, Ogasawara H, Näslund L, Hirsch TK, Ojamäe L, Glatzel P, Pettersson LG, Nilsson A (2004) The structure of the first coordination shell in liquid water. Science 304:995–999CrossRefPubMedGoogle Scholar
  2. 2.
    Head-Gordon T, Hura G (2002) Water structure from scattering experiments and simulations. Chem Rev 102:2651–2670CrossRefPubMedGoogle Scholar
  3. 3.
    Cheng YK, Rossky P (1998) Surface topography dependence of biomolecular hydrophobic hydration. Nature 392:696–699CrossRefPubMedGoogle Scholar
  4. 4.
    Fernández A (2013) The principle of minimal episteric distortion of the water matrix and its steering role in protein folding. J Chem Phys 139:085101CrossRefPubMedGoogle Scholar
  5. 5.
    Fernández A (2012) Epistructural tension promotes protein associations. Phys Rev Lett 108:188102CrossRefPubMedGoogle Scholar
  6. 6.
    Giovambattista N, Lopez CF, Rossky P, Debenedetti P (2008) Hydrophobicity of protein surfaces: separating geometry from chemistry. Proc Natl Acad Sci USA 105:2274–2279CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Debye P (1929) Polar molecules. Dover Publications, New YorkGoogle Scholar
  8. 8.
    Strekalova EG, Mazza MG, Stanley HE, Franzese G (2011) Large decrease of fluctuations for supercooled water in hydrophobic nanoconfinement. Phys Rev Lett 106:145701CrossRefPubMedGoogle Scholar
  9. 9.
    Tanizaki S, Feig F (2005) A generalized Born formalism for heterogeneous dielectric environments: application to the implicit modeling of biological membranes. J Chem Phys 122:124706CrossRefPubMedGoogle Scholar
  10. 10.
    Stanley HE, Buldyrev SV, Kumar P, Mallamace F, Mazza MG, Stokely K, Xu L, Franzese G (2011) Water in nanoconfined and biological environments. J Non-Cryst Solids 357:629–640CrossRefGoogle Scholar
  11. 11.
    Kumar P, Han S, Stanley HE (2009) Anomalies of water and hydrogen bond dynamics in hydrophobic nanoconfinement. J Phys Condens Matter 21:504108CrossRefPubMedGoogle Scholar
  12. 12.
    Fernández Stigliano A (2013) Breakdown of the Debye polarization ansatz at protein-water interfaces. J Chem Phys 138:225103CrossRefPubMedGoogle Scholar
  13. 13.
    Fernández A (2010) Transformative concepts for drug design: target wrapping. Springer, BerlinCrossRefGoogle Scholar
  14. 14.
    Schutz CN, Warshel A (2001) What are the dielectric “constants” of proteins and how to validate electrostatic models? Proteins-Struct Funct Gen 44:400–408CrossRefGoogle Scholar
  15. 15.
    Fernández A (2014) Fast track communication: water promotes the sealing of nanoscale packing defects in folding proteins. J Phys Chem Condens Matter 26:202101CrossRefGoogle Scholar
  16. 16.
    Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223–230CrossRefPubMedGoogle Scholar
  17. 17.
    Fernández A, Sosnick TR, Colubri A (2002) Dynamics of hydrogen-bond desolvation in folding proteins. J Mol Biol 321:659–675CrossRefPubMedGoogle Scholar
  18. 18.
    Chandler D (2005) Interfaces and the driving force of hydrophobic assembly. Nature 437:640–647CrossRefPubMedGoogle Scholar
  19. 19.
    Jewett A, Pande VS, Plaxco KW (2003) Cooperativity, smooth energy landscapes and the origins of topology-dependent protein folding rates. J Mol Biol 326:247–253Google Scholar
  20. 20.
    Scalley-Kim M, Baker D (2004) Characterization of the folding energy landscapes of computer generated proteins suggests high folding free energy barriers and cooperativity may be consequences of natural selection. J Mol Biol 338:573–583CrossRefPubMedGoogle Scholar
  21. 21.
    Fernández A, Colubri A, Berry RS (2002) Three-body correlations in protein folding: the origin of cooperativity. Phys A 307:235–259CrossRefGoogle Scholar
  22. 22.
    Fernández A, Kostov K, Berry RS (1999) From residue matching patterns to protein folding topographies: general model and bovine pancreatic trypsin inhibitor. Proc Natl Acad Sci USA 96:12991–12996CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Fernández A, Colubri A, Berry RS (2000) Topology to geometry in protein folding: beta-lactoglobulin. Proc Natl Acad Sci USA 97:14062–14066Google Scholar
  24. 24.
    Fernández A, Kardos J, Goto J (2003) Protein folding: could hydrophobic collapse be coupled with hydrogen-bond formation? FEBS Lett 536:187–192CrossRefPubMedGoogle Scholar
  25. 25.
    Fernández A (2001) Conformation-dependent environments in folding proteins. J Chem Phys 114:2489–2502CrossRefGoogle Scholar
  26. 26.
    Fernández A, Kardos J, Scott R, Goto Y, Berry RS (2003) Structural defects and the diagnosis of amyloidogenic propensity. Proc Natl Acad Sci USA 100:6446–6451CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Fernández A (2004) Keeping dry and crossing membranes. Nat Biotech 22:1081–1084CrossRefGoogle Scholar
  28. 28.
    Pietrosemoli N, Crespo A, Fernández A (2007) Dehydration propensity of order-disorder intermediate regions in soluble proteins. J Proteome Res 6:3519–3526CrossRefPubMedGoogle Scholar
  29. 29.
    Fernández A, Scott R (2003) Dehydron: a structure-encoded signal for protein interactions. Biophys J 85:1914–1928CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Avbelj F, Baldwin RL (2003) Role of backbone solvation and electrostatics in generating preferred peptide backbone conformations: distributions of phi. Proc Natl Acad Sci USA 100:5742–5747CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Krantz BA, Moran LB, Kentsis A, Sosnick TR (2000) D/H amide kinetic isotope effects reveal when hydrogen bonds form during protein folding. Nat Struct Biol 7:62–71CrossRefPubMedGoogle Scholar
  32. 32.
    Fersht A (2000) Transition-state structure as a unifying basis in protein-folding mechanisms: contact order, chain topology, stability, and the extended nucleus mechanism. Proc Natl Acad Sci USA 97:1525–1929CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Plaxco KW, Simmons KT, Baker D (1998) Contact order, transition state placement and the refolding rates of single domain proteins. J Mol Biol 277:985–994Google Scholar
  34. 34.
    Fernández A, Scott LR (2003) Adherence of packing defects in soluble proteins. Phys Rev Lett 91:018102CrossRefPubMedGoogle Scholar
  35. 35.
    Fernández A, Zhang X, Chen J (2008) Folding and wrapping soluble proteins: exploring the molecular basis of cooperativity and aggregation. Prog Nucleic Acid Res Trans Sci 83:57–87Google Scholar
  36. 36.
    Fernández A, Scheraga HA (2003) Insufficiently dehydrated hydrogen bonds as determinants of protein interactions. Proc Natl Acad Sci USA 100:113–118CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Fernández A, Berry RS (2003) Proteins with H-bond packing defects are highly interactive with lipid bilayers: implications for amyloidogenesis. Proc Natl Acad Sci USA 100:2391–2396CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Deremble C, Lavery R (2005) Macromolecular recognition. Curr Opin Struct Biol 15:171–175CrossRefPubMedGoogle Scholar
  39. 39.
    Ma B, Elkayam T, Wolfson H, Nussinov R (2003) Protein-protein interactions: structurally conserved residues distinguish between binding sites and exposed protein surfaces. Proc Natl Acad Sci USA 100:5772–5777CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Fernández A (2003) What caliber pore is like a pipe? Nanotubes as modulators of ion gradients. J Chem Phys 119:5315–5319CrossRefGoogle Scholar
  41. 41.
    Despa F, Fernández A, Berry RS (2004) Dielectric modulation of biological water. Phys Rev Lett 93:228104CrossRefPubMedGoogle Scholar
  42. 42.
    Demetri G (2002) Efficacy and safety of imatinib mesyalte in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480CrossRefPubMedGoogle Scholar
  43. 43.
    Fernández A, Sanguino A, Peng Z, Ozturk E, Chen J, Crespo A, Wulf S, Shavrin A, Qin C, Ma J, Trent J, Lin Y, Han HD, Mangala LS, Bankson JA, Gelovani J, Samarel A, Bornmann W, Sood AK, Lopez-Berestein G (2007) An anticancer c-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic. J Clin Invest 117:4044–4054CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Baldwin RL (2003) In search of the energetic role of peptide hydrogen bonds. J Biol Chem 278:17581–17588CrossRefPubMedGoogle Scholar
  45. 45.
    Powers ET, Deechongkit S, Kelly JW (2006) Backbone-backbone H-bonds make context-dependent contributions to protein folding kinetics and thermodynamics: lessons from amide-to-ester mutations. In: Baldwin RL, Baker D (eds) Peptide solvation and H-bonds, vol 72. Elsevier Academic Press, San Diego, 40–79 (Adv Prot Chem)Google Scholar
  46. 46.
    MacKinnon R, Reinhart PH, White MN (1988) Charybdotoxin block of Shaker K+ channels suggests that different types of K+ channels share common features. Neuron 1:997–1001CrossRefPubMedGoogle Scholar
  47. 47.
    Fernández A, Berry RS (2009) Golden rule for buttressing vulnerable soluble proteins. J Proteome Res 9:2643–2648CrossRefGoogle Scholar
  48. 48.
    Kumar MD (2006) ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions. Nucleic Acids Res 34:D204–D206CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Doig AJ, Williams DH (1991) Is the hydrophobic effect stabilizing or destabilizing in proteins: the contribution of disulfide bonds to protein stability. J Mol Biol 217:389–398CrossRefPubMedGoogle Scholar
  50. 50.
    Betz SF (1993) Disulfide bonds and the stability of globular proteins. Protein Sci 2:1551–1558CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.National Research Council–CONICETBuenos AiresArgentina
  2. 2.Former Karl F. Hasselmann Endowed Chair Professor of BioengineeringRice UniversityHoustonUSA

Personalised recommendations