Effect of trehalose on protein structure

Abstract

Trehalose is a ubiquitous molecule that occurs in lower and higher life forms but not in mammals. Till about 40 years ago, trehalose was visualized as a storage molecule, aiding the release of glucose for carrying out cellular functions. This perception has now changed dramatically. The role of trehalose has expanded, and this molecule has now been implicated in a variety of situations. Trehalose is synthesized as a stress-responsive factor when cells are exposed to environmental stresses like heat, cold, oxidation, desiccation, and so forth. When unicellular organisms are exposed to stress, they adapt by synthesizing huge amounts of trehalose, which helps them in retaining cellular integrity. This is thought to occur by prevention of denaturation of proteins by trehalose, which would otherwise degrade under stress. This explanation may be rational, since recently, trehalose has been shown to slow down the rate of polyglutamine-mediated protein aggregation and the resultant pathogenesis by stabilizing an aggregation-prone model protein. In recent years, trehalose has also proved useful in the cryopreservation of sperm and stem cells and in the development of a highly reliable organ preservation solution. This review aims to highlight the changing perception of the role of trehalose over the last 10 years and to propose common mechanisms that may be involved in all the myriad ways in which trehalose stabilizes protein structures. These will take into account the structure of trehalose molecule and its interactions with its environment, and the explanations will focus on the role of trehalose in preventing protein denaturation.

Figures

Figure 1

Transformation path of trehalose forms. Dihydrate trehalose Th is formed at equilibrium from the solution state and can be transformed reversibly to Tα. In addition, depending on the temperature and rate of water loss, Th can give either an amorphous form or the Tγ form. Reprinted from Ref. , with permission from Elsevier.

Figure 2

Various theories to explain the “exceptional” properties of trehalose. (A) Vitrification theory assumes that trehalose forms a glassy matrix that acts as a cocoon and presumably physically shields the protein or indeed cells from abiotic stresses. (B) Preferential exclusion theory, on the other hand, proposes that there is no direct interaction between trehalose and protein (or biomolecule). Instead, as can be seen, addition of trehalose to bulk water sequesters water molecules away from the protein, decreasing its hydrated radius and increasing its compactness and consequently stability. (C) Water replacement theory talks of substitution of water molecules by trehalose-forming hydrogen bonds, maintaining the three-dimensional structure and stabilizing biomolecules.