Molecular chaperones are ATP-consuming machines, which facilitate the folding of proteins and RNA molecules that are kinetically trapped in misfolded states. Unassisted folding occurs by the kinetic partitioning mechanism according to which folding to the native state, with low probability as well as misfolding to one of the many metastable states, with high probability, occur rapidly. GroEL is an all-purpose stochastic machine that assists misfolded substrate proteins to fold. The RNA chaperones such as CYT-19, which are ATP-consuming enzymes, help the folding of ribozymes that get trapped in metastable states for long times. GroEL does not interact with the folded proteins but CYT-19 disrupts both the folded and misfolded ribozymes. The structures of GroEL and RNA chaperones are strikingly different. Despite these differences, the iterative annealing mechanism (IAM) quantitatively explains all the available experimental data for assisted folding of proteins and ribozymes. Driven by ATP binding and hydrolysis and GroES binding, GroEL undergoes a catalytic cycle during which it samples three allosteric states, T (apo), R (ATP bound), and R″ (ADP bound). Analyses of the experimental data show that the efficiency of the GroEL-GroES machinery and mutants is determined by the resetting rate k R ″  → T , which is largest for the wild-type (WT) GroEL. Generalized IAM accurately predicts the folding kinetics of Tetrahymena ribozyme and its variants. Chaperones maximize the product of the folding rate and the steady-state native state fold by driving the substrates out of equilibrium. Neither the absolute yield nor the folding rate is optimized.

中文翻译：

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迭代退火机制解释了GroEL和RNA分子伴侣的功能。

分子伴侣是消耗ATP的机器，可促进蛋白质和RNA分子的折叠，这些蛋白质和RNA分子在动力学上处于错误折叠状态。通过动力学分配机制发生非辅助折叠，根据该动力学分配机制，迅速折叠到天然状态的可能性很低，并且错误折叠到许多亚稳状态之一的可能性很高。GroEL是一种多功能随机机器，可帮助错误折叠的底物蛋白质折叠。RNA伴侣（例如CYT-19）是消耗ATP的酶，有助于折叠被长期困在亚稳态的核酶。GroEL不与折叠的蛋白质相互作用，但CYT-19破坏折叠的和错误折叠的核酶。GroEL和RNA伴侣的结构截然不同。尽管有这些差异，迭代退火机制（IAM）定量解释了蛋白质和核酶辅助折叠的所有可用实验数据。在ATP结合，水解和GroES结合的驱动下，GroEL经历了一个催化循环，在此循环中，它采样了三个变构态T（脱辅基），R（与ATP结合）和R''（与ADP结合）。实验数据分析表明，GroEL-GroES机械和突变体的效率由重置率k R''→T决定，重置率k R''→T对野生型（WT）GroEL最大。通用IAM可以准确预测四膜虫核酶及其变体的折叠动力学。分子伴侣通过驱使底物失去平衡而使折叠速率和稳态自然折叠的乘积最大化。绝对产量和折叠率均未优化。