Dynamics Changes in the Molten Globule to Native Folding Step by Quasielastic Neutron Scattering

Published

January 1, 2001

Author(s)

Z Bu, Dan A. Neumann, S H. Lee, Craig Brown, D M. Engelman, Charles C. Han

Abstract

In order to understand the changes in protein dynamics that occur in the final stages of protein folding, we have used neutron scattering to probe the differences between a protein in its folded and the molten globule states. The internal dynamics of bovine alpha-lactalbumin (BLA) and its molten globules (MBLA) have been examined using incoherent, quasielastic neutron scattering (IQNS). On the length scale from 3.3 to 60 , our results show a length scale dependent, picosecond dynamics changes. On shorter length scales, the protons undergo jump motions over potential barriers such as those involved in side-chain rotamer changes, with the potential energy barriers to motions within BLA being higher than within the molten globule as might be expected; on longer length scales, the motion of the non-exchangeable protons can be described as spatially restricted diffusive motion, with the motion being more restricted in BLA than in MBLA. Thus, restrictions to both long-range and local motions help to maintain the native structure. At high frequency, both forms of the protein have similar mean square amplitudes, suggesting that the high frequency vibrational motions do not change significantly to folding. Interestingly, the quasi-elastic scattering intensities show a pronounced maximum at different positions, suggesting that a cluster of atoms at 4.4 distance apart for BLA and 5.7 for MBLA are moving collectively on pico-second time scales. The size of the atom cluster moving collectively is dramatically reduced in the molten globule with a correlation length of 6.9 compared with the correlation length of about 18 in the native protein. Such collective motions may be important for the stability of the folded state, and may influence the folding pathways from the molten globule.

Citation

Journal of Molecular Biology

Volume

80 No. 1

Pub Type

Journals

Keywords

alpha-lactalbumin, molten globule, protein dynamics, protein folding dynamics, quasielastic neutron scattering

Citation

Bu, Z. , Neumann, D. , Lee, S. , Brown, C. , Engelman, D. and Han, C. (2001), Dynamics Changes in the Molten Globule to Native Folding Step by Quasielastic Neutron Scattering, Journal of Molecular Biology (Accessed April 18, 2024)