Structural biology: analysis of protein-folding cooperativity.

Abstract

The folding of small proteins has been assumed to be an all-or-none process that involves high cooperativity within the structure and substantial kinetic-energy barriers. Sadqi et al. claim that the small re-engineered protein Naf-BBL unfolds without significant cooperativity or kinetic hindrance, a conclusion that is based on calculation of a broad distribution of midpoint thermal-transition temperatures measured by the nuclear magnetic resonance (NMR) chemical shifts of 158 protons. We find that all of the unprocessed melting curves can be fitted to the same two-state global unfolding when uncertainties in the experimental data are taken into account. We conclude that the authors' melting data for Naf-BBL remain consistent with the all-or-none process.