A partly folded state of acidic fibroblast growth factor at low pH

Acid denaturation of acidic fibroblast growth factor (aFGF) at low ionic strength was monitored by far-ultraviolet circular dichroism and intrinsic fluorescence. The two spectroscopic probes displayed non-coincident transitions, which suggested the accumulation of partly folded species around pH 4.0. Although under these conditions the fluorescence of aFGF resembled that of the unfolded form of the protein, far-ultraviolet 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 and interacted weakly with the hydrophobic probe N-phenyl-1-naphthylamine, showing a relatively high level of structure that did not fit into the classical molten globule category. This intermediate is also capable of interacting with liposomes and might represent a membrane translocation-competent form.