Binding of molten globule-like conformations to lipid bilayers. Structure of native and partially folded alpha-lactalbumin bound to model membranes.

The effect of membrane binding on the structure and stability of several conformers of alpha-lactalbumin was studied by infrared spectroscopy, circular dichroism, and fluorescence spectroscopy. In solution, under experimental conditions where all conformers interact with negatively charged membranes, they show significant conformational differences. However, binding to negatively charged membranes, which causes considerable changes in the structure of these conformers, leads to a remarkably similar protein conformation. The membrane-associated conformations are characterized by 1) a high helical content, greater than any of those found in solution, 2) a lack of stable tertiary structure, and 3) the disappearance of their thermotropic transition. These observations indicate that association with negatively charged membranes induces a conformational change within alpha-lactalbumin to a flexible, molten globule-like state.