RATE OF BETA-STRUCTURE FORMATION IN POLYPEPTIDES
RATE OF BETA-STRUCTURE FORMATION IN POLYPEPTIDES
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DOI：
10.1002/prot.340090104
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发表时间：
1991-01-01
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影响因子：
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通讯作者：
FINKELSTEIN, AV
中科院分区：
文献类型：
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作者：
FINKELSTEIN, AV
对于为什么略微稳定的贝塔结构折叠速度极慢提出了解释；据预测，即使是稳定性的微小增加也会急剧加速贝塔折叠。根据理论，这种折叠是一级相变，限速步骤是成核。决定速率的“核”(过渡态)是最小的β-折叠，其大小足以在随后的折叠过程中提供整体自由能降低。如果β结构的稳定性低，则原子核较大，并且由于具有较大的周长而具有较高的自由能。当最终的β-结构的净稳定性增加时(由于β-折叠稳定性的增加或竞争结构的稳定性的降低，例如，α-螺旋)，核的大小和能量减小，折叠速度指数增加。这必须导致由β-形成残基(例如，蛋白链)富含的多肽的快速折叠。该理论是为分子内β-结构而发展的，但它也可以解释分子间β-折叠的总体特征；它既适用于反平行的β-折叠，也适用于平行的β-折叠。讨论了β-折叠、α-螺旋和蛋白质在折叠过程中的差异。
An explanation is suggested for why a marginally stable beta-structure folds extremely slowly; it is predicted that even a small increase in stability drastically accelerates beta-folding. According to the theory, this folding is a first-order phase transition, and the rate-limiting step is nucleation. The rate-determining "nucleus" (transition state) is the smallest beta-sheet that is sufficiently large to provide an overall free energy reduction during subsequent folding. If the stability of the beta-structure is low, the nucleus is large and possesses a high free energy due to having a large perimeter. When the net stability of the final beta-structure increases (due to either an increase of the beta-sheet stability or a decrease in stability of the competing structures, e.g., alpha-helices), the size and energy of a nucleus decrease and the rate of folding increases exponentially. This must result in a fast folding of polypeptides enriched by beta-forming residues (e.g., protein chains). The theory is developed for intramolecular beta-structure, but it can also explain the overall features of intermolecular beta-folding; it is applicable both to antiparallel and parallel beta-sheets. The difference in folding of beta-sheets, alpha-helices, and proteins is discussed.