Dynamics of allosteric transitions in GroEL

被引:130
作者
Hyeon, Changbong
Lorimer, George H. [1 ]
Thirumalai, D.
机构
[1] Univ Maryland, Biophys Program Inst Phys Sci & Technol, College Pk, MD 20742 USA
[2] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
关键词
allostery; self-organized polymer model;
D O I
10.1073/pnas.0608759103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:18939 / 18944
页数:6
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