The role of disaccharides for protein–protein interactions – a SANS study

Abstract

The disaccharide trehalose has shown outstanding anti-aggregation properties for proteins, which are highly important for the possibility to treat neurodegenerative diseases, such as Alzheimer's and Huntington's disease. However, the role and mechanism of trehalose for such stabilising effects are still largely unknown, partly because a direct structural picture of how trehalose organises around proteins in an aqueous system is missing. Here we compare small-angle neutron scattering (SANS) data on myoglobin in aqueous solutions of either sucrose or trehalose, in order to investigate their effect on protein-protein interactions. We find that both trehalose and sucrose induces a well-defined protein-protein distance, which could explain why these inhibit protein-protein interactions and associated protein aggregation. It does not however explain the superior antiaggregation effect of trehalose and suggests that the local solvent structures are highly important for explaining the protein stabilisation mechanism. In a broader perspective, these findings are important for understanding the role of sugars in biological stabilisation, and could provide a structural explanation for why trehalose is a promising candidate for the treatment of neurodegenerative and other protein aggregation related diseases.

Stabilization of proteins embedded in sugars and water as studied by dielectric spectroscopy

“…That study was conducted at even lower water contents than in the present study, and is therefore not directly comparable; at too high S/P ratios the detrimental effect most likely stems from a microphase separation to high sugar domains and high protein domains, as shown in ref. 82 and 83. In the present study, the water content at the highest S/P ratios is relatively high, and thus such inhomogeneities should not be present to a large extent (as indicated by a previous study by our group 84 ), and the fast dynamics (and the protein stabilization by extension) in these samples is dominated by the water dynamics. However, the present samples containing 33 and 56 wt% myoglobin are comparable with the samples in the study by Giuffrida et al (albeit still at a higher water content here).…”

The Effect of Trehalose Coating for Magnetite Nanoparticles on Stability of Egg White Lysozyme

“…In addition, according to Figure 5 c,d, the Fe 3 O 4 @Tre NPs are better stabilizers for the protein structure, and they can be a structure-maker in HEWL. The presence of Tre around protein molecules prevents direct protein–protein interactions and stabilizes the colloidal stability of the protein [ 12 ]. However, at concentrations higher than CRT, the polarity of the environment around the protein is altered.…”

“…Although there are a number of methods such as dilution and dialysis for the recovery of aggregated proteins, most of them are not 100% efficient and cannot be used at concentrations higher than 0.1 mg mL −1 [ 10 , 11 ]. Factors such as the interactions between proteins [ 12 ], changes in the hydrophobicity and hydrophilicity of the surface of the protein, and physical and chemical [ 13 ] properties of the surface cause protein aggregation and the instability of the protein structure. However, the mechanism of these changes is not yet well understood.…”

Biotechnological techniques for intensification of protein extraction from the porcine pancreas

“…It is assumed that trehalose induces the well-defined protein-protein distance, which can explain why it inhibits protein-protein interactions and protein aggregation associated with them. However, the excellent anti-aggregation effect of trehalose can also be linked with the fact that the local solvent structures are very important for explaining the mechanism of protein stabilization [21]. The recommended initial concentration of 0.5 М for trehalose and sucrose [15,17] was used in this work.…”