Real-time NMR kinetic studies provide global and residue-specific information on the non-cooperative unfolding of the beta-trefoil protein, interleukin-1beta.

The interleukin-1beta (IL-1beta) structural motif is a beta-trefoil super fold created by six two-stranded beta-hairpins. Turns are thus particularly important in creating the topology and the arrangement of beta-strands in this structural motif. In contrast to the signals observed in optical studies, real-time NMR kinetic investigations of the denaturant-induced unfolding of interleukin-1beta provide direct, global, and residue-specific information on the structural nature of the unfolding reaction. Heterogeneity in the individual amino acid residue kinetics reveals a rugged unfolding landscape. The relative kinetic stability of native-like turns supports low temperature molecular dynamics predictions of turn-controlled unfolding.