Thermal stability of lysozyme as a function of ion concentration: A reappraisal of the relationship between the Hofmeister series and protein stability

Abstract

Anion and cation effects on the structural stability of lysozyme were investigated using differential scanning calorimetry. At low concentrations (<5 mM) anions and cations alter the stability of lysozyme but they do not follow the Hofmeister (or inverse Hofmeister) series. At higher concentrations protein stabilization follows the well-established Hofmeister series. Our hypothesis is that there are three mechanisms at work. At low concentrations the anions interact with charged side chains where the presence of the ion can alter the structural stability of the protein. At higher concentrations the low charge density anions perchlorate and iodide interact weakly with the protein. Their presence however reduces the Gibbs free energy required to hydrate the core of the protein that is exposed during unfolding therefore destabilizing the structure. At higher concentrations the high charge density anions phosphate and sulfate compete for water with the protein as it unfolds increasing the Gibbs free energy required to hydrate the newly exposed core of the protein therefore stabilizing the structure.

Lysozyme stability and amyloid fibrillization dependence on Hofmeister anions in acidic pH

“…Hofmeister anions significantly affect stability of protein [18,48]. An effect of anions on stability of HEWL at acidic pH was studied by DSC (Fig.…”

“…HEWL is basic protein with pI ~11.2 with net charge +19 at pH < 3 (11 from arginines, 6 from lysines, 1 from histidine, and 1 from N-terminal amine group) [15,16]. Thermal transition of HEWL at neutral pH is a highly cooperative and reversible two-state transition with T trs ~ 73 °C [17,18]. At acidic pH, at which the fibrillization of the protein is studied, its conformational properties as well as its stability will very likely strongly depend on the present anions.…”

Structural Stability of Streptococcal Serum Opacity Factor

“…This loss of activity is in the same range in which many common globular proteins, including albumin, are irreversibly denatured [14] but at a lower temperature range than that of lysozyme [15]. Thus, the thermal stability of SOF is not distinct from those of many other globular proteins.…”

pKA in proteins solving the Poisson–Boltzmann equation with finite elements

“…Modeling the environment of the protein is a crucial step in characterizing its electrostatics . Such environmental factors are temperature, pH, and ion concentration . Proteins have different pH optima to fulfill their functionality .…”

“…Routinely and for many years, the well‐established finite difference (FD) method is used to compute electrostatic energies of proteins . As accurate electrostatic energy computations for proteins are CPU‐time demanding and this in particular if the proteins are very large, we developed with m olecular F inite E lement S olver (mFES) an alternative method, which uses the Finite Element (FE) method to compute electrostatic potentials with the same accuracy but less degrees of freedom.…”