Dynamic regimes and correlated structural dynamics in native and denatured alpha-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 native and the denatured alpha-lactalbumin. The quasielastic scattering intensity shows that there are alpha-helical structure and tertiary-like side-chain interactions fluctuating on sub-nanosecond time-scales under extremely denaturing conditions and even in the absence of disulfide bonds. Based on the length-scale dependence of the decay rate of the measured correlation functions, the nanosecond dynamics of the native and the variously denatured proteins have three dynamic regimes. When 0.05<Q<0.5 A(-1) (where the scattering vector, Q, is inversely proportional to the length-scale), the decay rate, Gamma, shows a power law relationship, Gamma proportional to Q(2.42+/-0.08), that is analogous to the dynamic behavior of a random coil. However, when 0.5<Q<1.0 A(-1), the decay rate exhibits a Gamma proportional to Q(1.0+/-0.2) relationship. The effective diffusion constant of the protein decreases with increasing Q, a striking dynamic behavior that is not found in any chain-like macromolecule. We suggest that this unusual dynamics is due to the presence of a strongly attractive force and collective conformational fluctuations in both the native and the denatured states of the protein. Above Q>1.0 A(-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 barrier to side-chain proton jump motion is reduced in the molten globule and in the denatured proteins when compared to that of the native protein. Our results provide a dynamic view of the native-like topology established in the early stages of protein folding.
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NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-8562, USA. zimei.bu@nist.gov
Cook
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Callaway
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DJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004058:Diffusion; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry* / Q000378:metabolism*; D008027:Light; D008958:Models, Molecular; D009038:Motion; D009502:Neutrons; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D012997:Solvents; D014783:Viscosity
D012997:Solvents; D007768:Lactalbumin; D002118:Calcium