Ligand-free form of human alpha-fetoprotein: evidence for the molten globule state.

By means of circular dichroism and fluorescence spectroscopy, viscometry and scanning microcalorimetry we have shown that the release of ligands from human alpha-fetoprotein (AFP) results in a considerable rearrangement of the protein molecule. Ligand-free form is practically as compact as the native molecule and has native-like content of secondary structure but no rigid tertiary structure. This means that the release of ligands transforms the AFP molecule into a molten globule state. Stripping the ligands from AFP is the irreversible process, i.e., native protein molecule cannot be reconstituted from the ligand-free form of AFP by adding back ligands. A possible functional role of such a structural transformation is discussed.