STRUCTURE OF THE ACID STATE OF ESCHERICHIA-COLI RIBONUCLEASE HI

Under acidic conditions Escherichia coli ribonuclease HI (RNase H*) a dopts a partially folded state with all of the properties of a molten globule. Using amide hydrogen exchange carried out under acid state co nditions, followed by quenching and NMR detection on the native state, we have determined the residues that are responsible for the observed structure of the acid state. Although RNase H is a mixed alpha + bet a protein, a helical subdomain (helices A, D, and B) defines the struc ture of the acid state. This structure correlates with the rare higher energy conformations detected under native conditions and with data f or the earliest intermediates populated in the kinetic folding pathway of the protein.