Structural changes of alpha-lactalbumin induced by low pH and oleic acid.

The effects of low pH and oleic acid on conformation and association state of Ca2+-depleted bovine alpha-lactalbumin (apo-BLA) have been studied by electrospray ionization mass spectrometry, fluorescence spectroscopy, and circular dichroism. The experimental results demonstrate that two structurally distinct species exist in the conformational transition of apo-BLA induced by low pH. One species populates at pH 3.0 characterized as a monomeric molten globule state and the other accumulates at pH 4.0-4.5 which is a partially folded dimer. Oleic acid promotes the formation of the dimeric intermediate at pH 4.0 and 7.0, but increases the content of molten globule state remarkably at pH 3.0 compared with that in the absence of oleic acid, indicating that oleic acid at pH 3.0 plays a different role from those at pH 4.0 and 7.0. Our data provide insight into the mechanism of pH-dependent and oleic acid-dependent structural changes and oligomerization of alpha-lactalbumin, and will be helpful to the understanding of the apoptosis-inducing function of multimeric alpha-lactalbumin in which oleic acid is a necessary cofactor.