Creighton T E, Darby N J, Kemmink J
European Molecular Biology Laboratory, Heidelberg, Germany.
FASEB J. 1996 Jan;10(1):110-8. doi: 10.1096/fasebj.10.1.8566531.
Proteins can fold very rapidly, undoubtedly because they do not do so simply by random searching. The stable, partly folded species that can be detected during protein refolding are, however, of uncertain kinetic significance. The available kinetic evidence indicates that the intermediates that are most responsible for the rapidity of folding are extremely unstable and not populated detectably; they are less extreme versions of the transition state for folding. Protein folding is most readily studied when it is coupled to disulfide formation, which has the advantages that the intermediates can be characterized in detail and their kinetic roles determined unambiguously. The most important aspects of the disulfide folding pathway of BPTI are understood to at least a first approximation, and several other protein disulfide folding pathways are known in outline. These pathways demonstrate that disulfide folding is not intrinsically different from that not involving disulfide formation. Partly folded conformations can increase the rate of folding somewhat by causing productive disulfide bonds to be populated preferentially, but the most important folding intermediates are not detectable. The essence of folding is to build up the cooperativity between the individual interactions that is necessary for a stable conformation.
蛋白质能够非常迅速地折叠，这无疑是因为它们并非仅仅通过随机搜索来进行折叠。然而，在蛋白质重折叠过程中能够检测到的稳定的、部分折叠的物种，其动力学意义并不明确。现有的动力学证据表明，对折叠速度起主要作用的中间体极其不稳定，无法被检测到；它们是折叠过渡态的不太极端的形式。当蛋白质折叠与二硫键形成相关联时，最容易对其进行研究，这样做具有一些优点，即中间体能够被详细表征，并且它们的动力学作用能够被明确确定。抑肽酶二硫键折叠途径的最重要方面至少在初步近似程度上是已知的，并且其他几种蛋白质二硫键折叠途径也有大致了解。这些途径表明，二硫键折叠与不涉及二硫键形成的折叠在本质上没有区别。部分折叠的构象可以通过优先形成有效的二硫键来在一定程度上提高折叠速度，但最重要的折叠中间体是无法检测到的。折叠的本质是在各个相互作用之间建立起形成稳定构象所必需的协同性。
