Karanicolas John, Brooks Charles L
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Protein Sci. 2002 Oct;11(10):2351-61. doi: 10.1110/ps.0205402.
Topology has been shown to be an important determinant of many features of protein folding; however, the delineation of sequence effects on folding remains obscure. Furthermore, differentiation between the two influences proves difficult due to their intimate relationship. To investigate the effect of sequence in the absence of significant topological differences, we examined the folding mechanisms of segment B1 peptostreptococcal protein L and segment B1 of streptococcal protein G. These proteins share the same highly symmetrical topology. Despite this symmetry, neither protein folds through a symmetrical transition state. We analyzed the origins of this difference using theoretical models. We found that the strength of the interactions present in the N-terminal hairpin of protein L causes this hairpin to form ahead of the C-terminal hairpin. The difference in chain entropy associated with the formation of the hairpins of protein G proves sufficient to beget initiation of folding at the shorter C-terminal hairpin. Our findings suggest that the mechanism of folding may be understood by examination of the free energy associated with the formation of partially folded microstates.
拓扑结构已被证明是蛋白质折叠许多特征的重要决定因素；然而，序列对折叠影响的描述仍然不清楚。此外，由于这两种影响之间的密切关系，很难区分它们。为了在没有明显拓扑差异的情况下研究序列的影响，我们研究了肽链球菌蛋白L的B1片段和链球菌蛋白G的B1片段的折叠机制。这些蛋白质具有相同的高度对称拓扑结构。尽管具有这种对称性，但这两种蛋白质都不是通过对称的过渡态折叠的。我们使用理论模型分析了这种差异的起源。我们发现，蛋白质L的N端发夹中存在的相互作用强度导致该发夹比C端发夹更早形成。与蛋白质G的发夹形成相关的链熵差异足以导致在较短的C端发夹处开始折叠。我们的研究结果表明，通过检查与部分折叠微状态形成相关的自由能，可以理解折叠机制。
