A PARTLY FOLDED STATE OF ACIDIC FIBROBLAST GROWTH-FACTOR AT LOW PH

Acid denaturation of acidic fibroblast growth factor (aFGF) at low ion ic strength was monitored by far-ultraviolet circular dichroism and in trinsic fluorescence. The two spectroscopic probes displayed noncoinci dent transitions, which suggested the accumulation of partly folded sp ecies around pH 4.0. Although under these conditions the fluorescence of aFGF resembled that of the unfolded form of the protein, far-ultrav iolet circular dichroism and proton nuclear magnetic resonance spectra indicated the presence of persistent secondary and tertiary structure . Moreover, at pH 4.0, aFGF showed cooperative thermal denaturation an d interacted weakly with the hydrophobic probe N-phenyl-1-naphthylamin e, showing a relatively high level of structure that did not fit into the classical molten globule category. This intermediate is also capab le of interacting with liposomes and might represent a membrane transl ocation-competent form.