Cryo vs Thermo: Duality of Ethylene Glycol on the Stability of Proteins

Abstract

Osmolytes are known to stabilize proteins under stress conditions. Thermal denaturation studies on globular proteins (β-lactoglobulin, cytochrome c, myoglobin, α-chymotrypsin) in the presence of ethylene glycol (EG), a polyol class of osmolyte, demonstrate a unique property of EG. EG stabilizes proteins against cold denaturation and destabilizes them during heat-induced denaturation. Further, chemical denaturation experiments performed at room temperature and at a sub-zero temperature (−10 °C) show that EG stabilizes the proteins at subzero temperature but destabilizes them at room temperature. The experiments carried out in the presence of glycerol, however, showed that glycerol stabilizes proteins against all of the denaturing conditions. This differential effect has not been reported for any other polyol class of osmolyte and might be specific to EG. Moreover, molecular dynamics simulations of all of the four proteins were carried out at three different temperatures, 240, 300, and 340 K, in the absence and presence of EG (20 and 40%). The results suggest that EG preferably accumulates around the hydrophobic residues and reduces the hydrophobic hydration of the proteins at a low temperature leading to stabilization of the proteins. At 340 K, the preferential hydration of the proteins is significantly reduced and the preferential binding of EG destabilizes the proteins like common denaturants.

Imidazolium-based ionic liquids with increasing alkyl chain length of cations decrease the stability and fibrillation propensity of lysozyme

“…S9, ESI†), which can explain the energetics of the osmolyte-induced effect on the stabilization/destabilization of the protein. 68,69 The plot (Fig. 11) clearly indicates that the destabilization of ILs is enthalpy-driven in all cases.…”

ATP Can Efficiently Stabilize Protein through a Unique Mechanism

“…The behavior of protein under thermal perturbation and the impact of cosolvent have been widely studied by molecular dynamics (MD) simulations. − It was revealed through MD simulations that the unfolding process of lysozyme induced by high temperature begins in the highly flexible interdomain loop region. , As indicated in previous works, the osmolyte TMAO enhances the stability of lysozyme by altering the structure of bulk water. , A high concentration of TMAO (∼1000 mM) is required to sufficiently strengthen the hydrogen-bond network of aqueous solutions, thereby stabilizing protein. However, there has been limited work on the interactions between ATP and protein, leaving the molecular mechanism underlying how ATP enhances the protein stability with such great efficiency largely obscure.…”

Denaturation of proteins: electrostatic effects vs. hydration

“…41). The generalized van't Hoff equation used by these authors is based on eqn ( 17)- (19). Moreover, the dependence of the free energy of unfolding is assumed to be linear in c s as derived above in eqn (13):…”

“…8 There are many investigations that study the change of T m in the presence of various salts and non-charged solutes which can stabilize or destabilize the globular state. 4,6,7,[9][10][11][12][13][14][15][16][17][18][19][20] This effect is of obvious biological importance and can be traced back to hydration effects embodied in the Hofmeister series. [21][22][23][24] The collapse transition of poly(n-isopropylacrylamide) (PNIPAM) in aqueous solution is another well-studied and fundamental problem where a coiled polymer undergoes a transition from the coiled to the globular state with raising temperature.…”