Shortle D
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
FASEB J. 1996 Jan;10(1):27-34. doi: 10.1096/fasebj.10.1.8566543.
Experimental studies of the physical interactions that stabilize protein structure are complicated by the fact that proteins do not unfold to a simple reference state. When their folded structure breaks down, protein chains do not become random coils. Instead, they enter a poorly understood ensemble of partially folded states known collectively as the denatured state. Although it has long been held that agents that promote protein unfolding act specifically on the denatured state, the idea that mutations can exert their destabilizing (or in some cases, stabilizing) effects directly on this state is not widely accepted. A large body of thermodynamic data on mutant proteins plus a limited amount of structural information describing mutational effects on denatured states indicate that 1) the denatured state plays a central role in all aspects of protein stability, including mutant effects, and 2) a quantitative understanding of how amino acid sequence encodes protein structure will probably depend on a more complete picture of this complex, difficult-to-study state.
稳定蛋白质结构的物理相互作用的实验研究因蛋白质不会展开成简单的参考状态这一事实而变得复杂。当它们的折叠结构瓦解时，蛋白质链不会变成无规卷曲。相反，它们进入了一个知之甚少的部分折叠状态的集合，统称为变性状态。尽管长期以来人们一直认为促进蛋白质展开的试剂专门作用于变性状态，但突变可直接对该状态施加其不稳定（或在某些情况下，稳定）作用的观点并未被广泛接受。大量关于突变蛋白的热力学数据以及描述突变对变性状态影响的有限结构信息表明：1）变性状态在蛋白质稳定性的各个方面都起着核心作用，包括突变效应；2）对氨基酸序列如何编码蛋白质结构的定量理解可能取决于对这个复杂且难以研究的状态的更完整认识。
