Role of water in the formation of macromolecular structures

Abstract

This review shows that water in biological systems is not just a passive liquid solvent but also a partner in the formation of the structure of proteins, nucleic acids and their complexes, thereby contributing to the stability and flexibility required for their proper function. Reciprocally, biological macromolecules affect the state of the water contacting them, so that it is only partly in the normal liquid state, being somewhat ordered when bound to macromolecules. While the compaction of globular proteins results from the reluctance of their hydrophobic groups to interact with water, the collagen superhelix is maintained by water forming a hydroxyproline-controlled frame around this coiled-coil macromolecule. As for DNA, its stability and rigidity are linked to water fixed by AT pairs in the minor groove: this leads to the enthalpic contribution of AT pairs exceeding that of GC pairs, but this is overbalanced by their greater entropy contribution, with the result that AT pairs melt at lower temperatures than GCs. Loss of this water drives transcription factor binding to the minor groove.

Keywords: DNA; Hydration; Proteins; Tissues; Water.

Fig. 1

Distribution of charges in the water molecule (a) and its stereometry (b); c the structure of ice; d two possible positions for hydrogen localization in ice

Fig. 2

Temperature dependencies of the heat capacity of a frog muscle (Bella and Berman 1996); b solutions of DNA, collagen and hemoglobin containing 2 g of water per gram of biopolymer (Mrevlishvili and Privalov 1967); c, d collagen and DNA containing 0, 0.5, 0.75, 1.0 and 2.0 g of water per gram of macromolecule (Privalov and Mrevlishvili 1967)

Fig. 3

Partial specific heat capacity profiles of various globular proteins in solution having the indicated pH values (Privalov and Khechinashvili 1974)

Fig. 4

a The temperature dependencies of the enthalpy, entropy factor and Gibbs energy of myoglobin unfolding. b The DSC recorded heat effects upon cooling the myoglobin solution and its consecutive heating. c The calculated Gibbs energy functions of myoglobin in solutions with different pH. d Intrinsic viscosity of myoglobin in the solutions with different pH (Privalov et al. 1986)

Fig. 5

The DSC-measured partial heat capacity functions of myoglobin, apo-myoglobin and staphylococcal nuclease in solutions with different pH (Griko et al. , ; Privalov et al. 1986). With an increase of protein stability by raising the pH, the heat denaturation shifts to higher temperatures, while cold denaturation shifts to lower temperatures, as predicted by the thermodynamics (see Fig. 4c)

Fig. 6

Thermodynamics of a liquid hydrocarbon dissolving into water, assuming a constant heat capacity change (Privalov and Gill 1988)

Fig. 7

Contribution of the dissipative force [T∆S(T _x)] and the water solvation effect [∆C _p/2 (T _s − T)²/T] to the stabilization of an abstract globular protein (Privalov and Gill 1988)

Fig. 8

a A single strand of the repeated -Gly-Pro-Hyp- sequence in the poly-l proline conformation. b The three-stranded coiled coil. c The one-bonded model (Rich and Crick 1955); d the two-bonded mode (Ramachandran and Kartha 1955)

Fig. 9

a Breakdown of the collagen structure upon heating observed by drastic changes in the intrinsic viscosity and optical rotation (von Hippel 1967). b Plot of collagen melting temperature in salt-free solution at pH 3.7 versus the total imino acid content per 1000 residues (for details, see Privalov 1982)

Fig. 10

Temperature dependence of the partial specific heat capacity of cod (A), pike (B) and rat (C) skin collagens in pH 3.5 salt-free solution. A fragment at a magnified scale is presented under melting profiles to demonstrate the denaturational heat capacity increment, (Privalov 1982)

Fig. 11

Plot of the melting enthalpy of collagens (per mole of residue values, extrapolated to 25 °C) versus a the total prolyl and hydroxyprolyl content and b only hydroxyprolyl content in the helical parts of various species: 1 cod skin, 2 halibut, 3 frog skin, 4 pike skin, 5 carp swim bladder, 6 rat skin and 7 sheep skin (Privalov 1982)

Fig. 12

Crystal structure of a synthetic (Pro-Hyp-Gly) collagen-like triple helix. The three stands are in yellow, red and magenta and layers of fixed water molecules (in cyan) cover the triple-helix. Repetitive patterns of water bridges link oxygen atoms both within a single peptide chain, between different chains and even between different triple helices. Overall, the water molecules are organized in a semi-clathrate-like structure that surrounds and interconnects triple-helices in the crystal lattice (Bella et al. 1995)

Fig. 13

Plot of the melting temperature of collagens from various species versus the average physiological temperature of the species (squares). Also plotted are the upper limits for the physiological temperatures of the different species (circles). 1 Ice fish; 2 Antimora (violet cod); 3 cod; 4 Alepocephalus (slickhead fish); 5 whiting; 6 Allolobaphora caliginosa (earthworm); 7 earthworm; 8 flatfish; 9 Cyprinus carpio (carp); 10 butterfly fish; 11 tuna; 12 Rana tempararia (frog); 13 Aurelia coerula (jellyfish); 14 Rana ridibunda (frog); 15 Helix aspersa (snail); 16 rat; 17 human; 18 pig; 19 chicken (Privalov 1982)

Fig. 14

Comparison of the partial molar heat capacities of 9, 12 and 15 base pair CG duplexes (red) and the same length duplexes including AT pairs (blue), all at the identical molar concentration of 283 µM in 150 mM NaCl, 5 mM Na-phosphate, pH 7.0 (Vaitiekunas et al. 2015)

Fig. 15

The partial heat capacity functions of the three considered CG DNA duplexes calculated per mole of duplex (molar heat capacity, upper panel) and per mole of base pair (specific molar heat capacity, lower panel), all measured at the same molarity, 230 μM, of the duplexes in 150 mM NaCl, 5 mM Na-phosphate, pH 7.4. Inset the dependence of the excess enthalpy on the transition temperature, the slope of which gives an estimate of ∆C _p (Vaitiekunas et al. 2015)

Fig. 16

Contributions of CG and AT base pairs to the enthalpy (∆H), entropy factor (T∆S) and Gibbs energy (∆G) of the cooperative phase of DNA duplex dissociation. For more details, see Vaitiekunas et al. (2015)

Fig. 17

Display of primary (blue) and secondary (yellow) layers of the spine of water in the minor groove of the crosslinked dodecamer CGCGAATTCGCG, generated from the coordinates of NDB accession number BD0008 [reproduced from (Privalov et al. 2007)]

Fig. 18

Interaction of the DBDs of various transcription factors with their target DNA sequences at 20 °C in 10 mM potassium phosphate (pH 6.0), 100 mM KCl: a DNA bend angles induced b the Gibbs energy of binding, c the enthalpy of binding d, the entropy factor of binding (for details, see Privalov et al. 2007)

Fig. 19

The Lef86 DBD binding to DNA^Lef (the optimal target) and to DNA^Sry (a sub-optimal sequence). The identical slopes show that the same numbers of ionic contacts are made with both target sequences. The difference in log(K ^a) at log([KCl]) = 0 (and at every other KCl concentration) represents the difference in the non-electrostatic component of the interaction with the optimal and sub-optimal targets (Privalov et al. 2011)

Fig. 20

Enthalpies and entropy factors (non-electrostatic and electrostatic) of binding proteins to the minor and major groove of their optimal and sub-optimal DNAs at 20 °C in 10 mM potassium phosphate (pH 6.0), 100 mM KCl. For details, see Privalov et al. (2007)

Fig. 21

Partial molar heat capacity functions of WT SSI and the D83C mutant at different concentrations of protein in pH 6.0 solutions. Numbers in the box indicate concentrations of dimer in μM (Tamura and Privalov 1997)