Plaxco K W, Baker D
Department of Biochemistry, Box 357350, University of Washington, Seattle, WA 98195-7350, USA.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13591-6. doi: 10.1073/pnas.95.23.13591.
Small, single-domain proteins typically fold via a compact transition-state ensemble in a process well fitted by a simple, two-state model. To characterize the rate-limiting conformational changes that underlie two-state folding, we have investigated experimentally the effects of changing solvent viscosity on the refolding of the IgG binding domain of protein L. In conjunction with numerical simulations, our results indicate that the rate-limiting conformational changes of the folding of this domain are strongly coupled to solvent viscosity and lack any significant "internal friction" arising from intrachain collisions. When compared with the previously determined solvent viscosity dependencies of other, more restricted conformational changes, our results suggest that the rate-limiting folding transition involves conformational fluctuations that displace considerable amounts of solvent. Reconciling evidence that the folding transition state ensemble is comprised of highly collapsed species with these and similar, previously reported results should provide a significant constraint for theoretical models of the folding process.
小的单结构域蛋白通常通过紧密的过渡态集合体进行折叠，这一过程很好地符合简单的两态模型。为了表征两态折叠背后的限速构象变化，我们通过实验研究了改变溶剂粘度对蛋白L的IgG结合结构域重折叠的影响。结合数值模拟，我们的结果表明，该结构域折叠的限速构象变化与溶剂粘度紧密相关，并且不存在由链内碰撞引起的任何显著“内摩擦”。与先前确定的其他更受限构象变化的溶剂粘度依赖性相比，我们的结果表明，限速折叠转变涉及到使大量溶剂发生位移的构象波动。将折叠过渡态集合体由高度压缩的物种组成这一证据与这些以及先前报道的类似结果相协调，应该会为折叠过程的理论模型提供一个重要的约束条件。
