Exposure of thiol groups in the heat-induced denaturation of β-lactoglobulin

Abstract

Protein aggregates can be stabilised by disulphide bridges. The whey protein β-lactoglobulin (β-lac) contains a disulphide bridge and a free cysteine that are shielded from the solvent by an α-helix. These groups are important in the thiol–disulphide exchange that occurs during aggregation and gelation of β-lac. Replica exchange molecular dynamics simulations show that the exposure mechanism is very different for the two buried groups. While melting of the α-helix enhances exposure of the free cysteine, it does not for the buried bridge. These findings shed light on the molecular mechanism of the first step of β-lac denaturation and aggregation.

Keywords::

• proteins
• replica exchange molecular dynamics
• aggregation

Acknowledgements

The authors thank R. Floris and I. Bodnár for stimulating discussions on the aggregation of β-lac. This work is part of the research programme of the Foundation for Fundamental Research on Matter, which is financially supported by the Netherlands Organisation for Scientific Research.