Ligand Concentration Regulates the Pathways of Coupled Protein Folding and Binding
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- 作者：Kyle G. Daniels ; Nam K. Tonthat ; David R. McClure ; Yu-Chu Chang ; Xin Liu ; Maria A. Schumacher ; Carol A. Fierke ; Scott C. Schmidler ; Terrence G. Oas
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：January 22, 2014
- 年：2014
- 卷：136
- 期：3
- 页码：822-825
- 全文大小：314K
- ISSN：1520-5126
文摘
Coupled ligand binding and conformational change plays a central role in biological regulation. Ligands often regulate protein function by modulating conformational dynamics, yet the order in which binding and conformational change occurs are often hotly debated. Here we show that the 鈥渃onformational selection versus induced fit鈥?distinction on which this debate is based is a false dichotomy because the mechanism depends on ligand concentration. Using the binding of pyrophosphate (PPi) to Bacillus subtilis RNase P protein as a model, we show that coupled reactions are best understood as a change in flux between competing pathways with distinct orders of binding and conformational change. The degree of partitioning through each pathway depends strongly on PPi concentration, with ligand binding redistributing the conformational ensemble toward the folded state by both increasing folding rates and decreasing unfolding rates. These results indicate that ligand binding induces marked and varied changes in protein conformational dynamics, and that the order of binding and conformational change is ligand concentration dependent.