Interaction of diphtheria toxin T domain with molten globule-like proteinsand its implications for translocation

The transmembrane (T) domain of diphtheria toxin has a critical role in the Low pH-induced translocation of the catalytic domain (A chain) of the toxi n across membranes. Here it is shown that at Low pH, addition of proteins i n a partly unfolded, molten globule-like conformation converted the T domai n from a shallow membrane-inserted form to its transmembrane form. Fluoresc ence energy transfer demonstrated that molten globule-like proteins bound t o the T domain. Thus, the T domain recognizes proteins that are partly unfo lded and may function in translocation of the A chain as a transmembrane ch aperone.