Bhutani N, Udgaonkar J B
National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, 5600065, India.
J Mol Biol. 2000 Apr 14;297(5):1037-44. doi: 10.1006/jmbi.2000.3648.
Despite extensive structural and kinetic studies, the mechanism by which the Escherichia coli chaperonin GroEL assists protein folding has remained somewhat elusive. It appears that GroEL might play an active role in facilitating folding, in addition to its role in restricting protein aggregation by secluding folding intermediates. We have investigated the kinetic mechanism of GroEL-mediated refolding of the small protein barstar. GroEL accelerates the observed fast (millisecond) refolding rate, but it does not affect the slow refolding kinetics. A thermodynamic coupling mechanism, in which the concentration of exchange-competent states is increased by the law of mass action, can explain the enhancement of the fast refolding rates. It is not necessary to invoke a catalytic role for GroEL, whereby either the intrinsic refolding rate of a productive folding transition or the unfolding rate of a kinetically trapped off-pathway intermediate is increased by the chaperonin.
尽管已经进行了广泛的结构和动力学研究，但大肠杆菌伴侣蛋白GroEL协助蛋白质折叠的机制仍有些难以捉摸。看来，GroEL除了通过隔离折叠中间体来限制蛋白质聚集的作用外，可能在促进折叠方面发挥积极作用。我们研究了GroEL介导的小蛋白巴氏抑素重折叠的动力学机制。GroEL加速了观察到的快速（毫秒级）重折叠速率，但不影响缓慢的重折叠动力学。一种热力学偶联机制，即通过质量作用定律增加可交换状态的浓度，可以解释快速重折叠速率的提高。没有必要赋予GroEL催化作用，即伴侣蛋白提高生产性折叠转变的固有重折叠速率或动力学捕获的非途径中间体的解折叠速率。
