SINGLE VERSUS PARALLEL PATHWAYS OF PROTEIN-FOLDING AND FRACTIONAL FORMATION OF STRUCTURE IN THE TRANSITION-STATE
SINGLE VERSUS PARALLEL PATHWAYS OF PROTEIN-FOLDING AND FRACTIONAL FORMATION OF STRUCTURE IN THE TRANSITION-STATE
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DOI：
10.1073/pnas.91.22.10426
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
OTZEN, DE
中科院分区：
文献类型：
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作者：
FERSHT, AR;ITZHAKI, LS;OTZEN, DE
蛋白质工程和动力学实验表明，蛋白质的某些区域在蛋白质折叠的过渡状态下部分形成结构。一个关键问题是，是否存在一个真正单一的过渡状态，其相互作用在这些区域被削弱，或者是否存在涉及许多过渡状态的平行路径，其中一些过渡状态的相互作用完全形成，另一些的结构要素完全展开。我们描述了一个动力学测试来区分这些可能性。动力学排除了涉及大麦胰凝乳蛋白酶抑制剂2和芽孢杆菌RNA酶区域的完全形成或完全展开结构的混合的机制，因此这些区域在过渡态下实际上仅部分折叠。讨论了蛋白质折叠途径建模的含义。
Protein engineering and kinetic experiments indicate that some regions of proteins have partially formed structure in the transition state for protein folding. A crucial question is whether there is a genuine single transition state that has interactions that are weakened in those regions or there are parallel pathways involving many transition states, some with the interactions fully formed and others with the structural elements fully unfolded. We describe a kinetic test to distinguish between these possibilities. The kinetics rule out those mechanisms that involve a mixture of fully formed or fully unfolded structures for regions of the barley chymotrypsin inhibitor 2 and barnase, and so those regions are genuinely only partially folded in the transition state. The implications for modeling of protein folding pathways are discussed.