迭代退火机制解释了GroEL和RNA伴侣的功能
Iterative Annealing Mechanism Explains the Functions of the GroEL and RNA Chaperones
摘要：
分子伴侣是消耗ATP的生物机器，其促进蛋白质和RNA分子的折叠，所述蛋白质和RNA分子在动力学上长时间被困在错误折叠状态。无辅助折叠通过动力学分配机制发生，根据动力学分配机制，以低概率折叠到天然状态以及以高概率错误折叠到许多亚稳态之一，在类似的时间尺度上迅速发生。GroEL是一种多用途的随机机器，可以帮助错误折叠的底物蛋白（SP）折叠。RNA分子伴侣（CYT-19）帮助容易错误折叠的核酶折叠。GroEL不与折叠的蛋白质相互作用，但CYT-19破坏折叠和错误折叠的核酶。尽管存在这一主要差异，迭代退火机制（IAM）定量地解释了蛋白质和核酶辅助折叠的所有可用实验数据。在ATP结合和水解以及GroES结合的驱动下，GroEL经历催化循环，在此期间，它采样三种变构状态，称为T（apo）、R（ATP结合）和R“（ADP结合）。与IAM预测一致，实验数据的分析表明GroEL-GroES机制和突变体的效率由重置速率$k_{R''\rightarrow T}$决定，其对于野生型GroEL是最大的。广义IAM精确预测了四膜虫核酶及其变体的折叠动力学。分子伴侣通过驱动底物脱离平衡而使折叠速率和稳态天然状态折叠的乘积最大化。绝对产率和折叠速率都没有优化。
英文摘要：
Molecular chaperones are ATP-consuming biological machines, which facilitate the folding of proteins and RNA molecules that are kinetically trapped in misfolded states for long times. 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 on similar time scales. GroEL is an all-purpose stochastic machine that assists misfolded substrate proteins (SPs) to fold. The RNA chaperones (CYT-19) help the folding of ribozymes that readily misfold. GroEL does not interact with the folded proteins but CYT-19 disrupts both the folded and misfolded ribozymes. Despite this major difference, 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, referred to as T (apo), R (ATP bound), and R'' (ADP bound). In accord with the IAM predictions, analyses of the experimental data shows that the efficiency of the GroEL-GroES machinery and mutants is determined by the resetting rate $k_{R''\rightarrow T}$, which is largest for the wild type 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.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
