Flexibility, functionality and hydrophobicity of bovine beta-lactoglobulin

Bovine beta-lactoglobulin is a globular protein that maintains a large solvent-exposed hydrophobic pocket, into which a variety of hydrophobic molecules, such as fatty acids, retinoids (e.g. vitamin A) and cholesterol, has been shown to bind. The protein, which belongs to the superfamily of lipocalins, comprises a very rigid eight-stranded primarily beta-barrel core and a number of very flexible loops connecting the beta strands. Protein three-dimensional structures derived from X-ray crystallographic and nuclear magnetic resonance spectroscopic studies are compared to ascertain intrinsic differences in the core structure under very different experimental conditions. A semi-quantitative model, based in part on surface free-energy minimization, is presented. It offers fresh insight into the critical structural role that the flexible loops play in providing entropic stabilization to the substantial entropic cost (similar to100 kJ mol(-1)) of maintaining the large hydrophobic pocket. (C) 2002 Elsevier Science Ltd. All rights reserved.