COMPARISON OF THE BACKBONE DYNAMICS OF A FOLDED AND AN UNFOLDED SH3 DOMAIN EXISTING IN EQUILIBRIUM IN AQUEOUS BUFFER

Two-dimensional NMR N-15 relaxation studies have been used to characte rize the backbone dynamics and folding transition of the N-terminal SH 3 domain of the protein drk (drkN SH3). The isolated drkN SH3 domain e xists in equilibrium between a folded and an unfolded state in aqueous buffer and near neutral pH [Zhang et al. (1994) J. Biomol. NMR 4, 845 ]. The backbone dynamics of both the folded and unfolded states in thi s exchanging system have been determined and the rates of the folding transition estimated at 14 degrees C, For 12 residues, the values of t he spectral density functions of the backbone amide bond vectors at a number of frequencies have been established. Results show that while t he unfolded state has considerably greater dynamic behavior, the overa ll motional properties are consistent with it having a reasonably comp act structure in solution. In contrast to the folded state, considerab le variations are seen in the values of the spectral densities of the unfolded state as a function of residue number; these variations do no t appear to be strongly correlated with structural elements in the fol ded state, The mean value of the exchange rate associated with the fol ding transition was determined to be 0.89 s(-1), similar to previous m easurements of the rate of formation of beta-structure.