Konishi Y, Ooi T, Scheraga H A
Proc Natl Acad Sci U S A. 1982 Sep;79(18):5734-8. doi: 10.1073/pnas.79.18.5734.
Two models of protein-folding pathways are proposed on the basis of equilibrium and kinetic data in the literature. One is a growth-type model--i.e., nucleation of the native-like structure occurs in the folding process, in the rate-limiting step(s), and subsequent folding around the nucleation sites proceeds smoothly to form the native disulfide bonds and conformation. The other is a rearrangement-type model--i.e., proper nucleation does not occur in the folding process; instead, non-native interactions play a significant role in the folding pathways and lead to metastable intermediate species. Such non-native interactions, including incorrect disulfide bonds and proline cis-trans isomerization, must be disrupted or rearranged to nucleate the native interactions [a process that is included in the rate-limiting step(s)] for the protein to fold. The rate-limiting steps in the pathways for regeneration of RNase A from the reduced protein are classified as growth- or rearrangement-type pathways. The growth-type pathway is the one accompanying the formation of an intramolecular disulfide bond in the rate-limiting step. The rearrangement-type pathway is the one accompanying the reshuffling or disruption of a disulfide bond in the rate-limiting step. The folding of other proteins, accompanying oxidation of the reduced form, and the folding of denatured proteins with intact disulfide bonds are discussed in terms of the growth- and rearrangement-type models.
基于文献中的平衡和动力学数据，提出了两种蛋白质折叠途径模型。一种是生长型模型，即类似天然结构的成核在折叠过程中的限速步骤中发生，随后围绕成核位点的折叠顺利进行，形成天然二硫键和构象。另一种是重排型模型，即折叠过程中不会发生适当的成核；相反，非天然相互作用在折叠途径中起重要作用，并导致亚稳中间体的形成。这种非天然相互作用，包括不正确的二硫键和脯氨酸顺反异构化，必须被破坏或重排，以使蛋白质折叠的天然相互作用成核（这一过程包含在限速步骤中）。从还原态蛋白质再生核糖核酸酶A的途径中的限速步骤被归类为生长型或重排型途径。生长型途径是在限速步骤中伴随着分子内二硫键形成的途径。重排型途径是在限速步骤中伴随着二硫键重排或破坏的途径。还根据生长型和重排型模型讨论了其他蛋白质在还原形式氧化时的折叠以及具有完整二硫键的变性蛋白质的折叠。
