DETECTION OF RARE PARTIALLY FOLDED MOLECULES IN EQUILIBRIUM WITH THE NATIVE CONFORMATION OF RNASEH

Despite the general observation that single domain proteins denature i n a completely cooperative manner, amide hydrogen exchange of ribonucl ease H in low levels of denaturant demonstrates the existence of two p artially folded species. The structures of these marginally stable spe cies resemble kinetic folding intermediates and the molten globule sta te of the protein. These data suggest that the first region to fold is the thermodynamically most stable portion of the protein and that the molten globule is a high free energy conformation present at equilibr ium in the native state.