THE KINETIC FOLDING INTERMEDIATE OF RIBONUCLEASE-H RESEMBLES THE ACIDMOLTEN GLOBULE AND PARTIALLY UNFOLDED MOLECULES DETECTED UNDER NATIVECONDITIONS

Folding of ribonuclease HI from Escherichia coli populates a kinetic i ntermediate detectable by stopped-flow circular dichroism. Pulse label ling hydrogen exchange reveals that this intermediate consists of a st ructured core region of the protein, namely helices A and D and beta-s trand 4. This kinetic intermediate resembles both the acid molten glob ule of ribonuclease HI and rarely populated, partially unfolded forms detected under native conditions. These results indicate that the firs t portion of ribonuclease HI to fold is the most thermodynamically sta ble region of the native state, and that folding of this protein follo ws a hierarchical process.