Plaxco K W, Simons K T, Baker D
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
J Mol Biol. 1998 Apr 10;277(4):985-94. doi: 10.1006/jmbi.1998.1645.
Theoretical studies have suggested relationships between the size, stability and topology of a protein fold and the rate and mechanisms by which it is achieved. The recent characterization of the refolding of a number of simple, single domain proteins has provided a means of testing these assertions. Our investigations have revealed statistically significant correlations between the average sequence separation between contacting residues in the native state and the rate and transition state placement of folding for a non-homologous set of simple, single domain proteins. These indicate that proteins featuring primarily sequence-local contacts tend to fold more rapidly and exhibit less compact folding transition states than those characterized by more non-local interactions. No significant relationship is apparent between protein length and folding rates, but a weak correlation is observed between length and the fraction of solvent-exposed surface area buried in the transition state. Anticipated strong relationships between equilibrium folding free energy and folding kinetics, or between chemical denaturant and temperature dependence-derived measures of transition state placement, are not apparent. The observed correlations are consistent with a model of protein folding in which the size and stability of the polypeptide segments organized in the transition state are largely independent of protein length, but are related to the topological complexity of the native state. The correlation between topological complexity and folding rates may reflect chain entropy contributions to the folding barrier.
理论研究表明，蛋白质折叠的大小、稳定性和拓扑结构与实现折叠的速率及机制之间存在关联。近期对一些简单单结构域蛋白质重折叠的表征提供了检验这些论断的方法。我们的研究揭示，对于一组非同源的简单单结构域蛋白质，天然状态下接触残基之间的平均序列间距与折叠速率及折叠过渡态位置之间存在统计学上的显著相关性。这些结果表明，主要以序列局部接触为特征的蛋白质往往折叠得更快，且与那些以更多非局部相互作用为特征的蛋白质相比，呈现出不太紧凑的折叠过渡态。蛋白质长度与折叠速率之间没有明显的关系，但在长度与过渡态中被掩埋的溶剂暴露表面积分数之间观察到微弱的相关性。平衡折叠自由能与折叠动力学之间，或化学变性剂与温度依赖性衍生的过渡态位置测量值之间预期的强相关性并不明显。观察到的相关性与一种蛋白质折叠模型一致，在该模型中，在过渡态中组织的多肽片段的大小和稳定性在很大程度上与蛋白质长度无关，但与天然状态的拓扑复杂性有关。拓扑复杂性与折叠速率之间的相关性可能反映了链熵对折叠屏障的贡献。
