Dynamics of allosteric transitions in GroEL.
The chaperonin GroEL-GroES, a machine that helps proteins to fold, cycles through a number of allosteric states, the T state, with high affinity for substrate proteins, the ATP-bound R state, and the R" (GroEL-ADP-GroES) complex. Here, we use a self-organized polymer model for the GroEL allosteric states and a general structure-based technique to simulate the dynamics of allosteric transitions in two subunits of GroEL and the heptamer. The T --> R transition, in which the apical domains undergo counterclockwise motion, is mediated by a multiple salt-bridge switch mechanism, in which a series of salt-bridges break and form. The initial event in the R -->R" transition, during which GroEL rotates clockwise, involves a spectacular outside-in movement of helices K and L that results in K80-D359 salt-bridge formation. In both the transitions there is considerable heterogeneity in the transition pathways. The transition state ensembles (TSEs) connecting the T, R, and R" states are broad with the TSE for the T --> R transition being more plastic than the R --> R" TSE.
Hyeon
Changbong
C
Biophysics Program Institute for Physical Science and Technology, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Lorimer
George H
GH
Thirumalai
D
D
D000494:Allosteric Regulation; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D018834:Chaperonin 60