Dynamic regimes and correlated structural dynamics in native and denaturedalpha-lactalbumin

Understanding the mechanisms of protein folding requires knowledge of both the energy landscape and the structural dynamics of a protein. We report a neutron-scattering study of the nanosecond and picosecond dynamics of nativ e and the denatured a-lactalbumin. The quasielastic scattering intensity sh ows that there are alpha -helical structure and tertiary-like side-chain in teractions fluctuating on sub-nanosecond time-scales under extremely denatu ring conditions and even in the absence of disulfide bonds. Based on the le ngth-scale dependence of the decay rate of the measured correlation functio ns, the nanosecond dynamics of the native and the variously denatured prote ins have three dynamic regimes. When 0.05 < Q < 0.5 Angstrom (-1) (where th e scattering vector, Q, is inversely proportional to the length-scale), the decay rate, F, shows a power law relationship, Gamma proportional to Q(2.4 2 +/- 0.08), that is analogous to the dynamic behavior of a random coil. Ho wever, when 0.5 < Q <1.0 Angstrom (-1), the decay rate exhibits a Gamma pro portional to Q(1.0 +/- 0.2) relationship. The effective diffusion constant of the protein decreases with increasing Q, a striking dynamic behavior tha t is not found in any chain-like macromolecule. We suggest that this unusua l dynamics is due to the presence of a strongly attractive force and collec tive conformational fluctuations in both the native and the denatured state s of the protein. Above Q > 1.0 Angstrom (-1) is a regime that displays the local dynamic behavior of individual residues, Gamma proportional to Q(1.8 +/- 0.3). The picosecond time-scale dynamics shows that the potential barr ier to side-chain proton jump motion is reduced in the molten globule and i n the denatured proteins when compared to that of the native protein. Our r esults provide a dynamic view of the native-like topology established in th e early stages of protein folding. (C) 2001 Academic Press.