Ligand concentration regulates the pathways of coupled protein folding and binding

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

研究成果: 雜誌貢獻文章

41 引文 斯高帕斯(Scopus)

摘要

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 "conformational selection versus induced fit" 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.
原文英語
頁(從 - 到)822-825
頁數4
期刊Journal of the American Chemical Society
136
發行號3
DOIs
出版狀態已發佈 - 一月 22 2014
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

引用此

Daniels, K. G., Tonthat, N. K., McClure, D. R., Chang, Y. C., Liu, X., Schumacher, M. A., Fierke, C. A., Schmidler, S. C., & Oas, T. G. (2014). Ligand concentration regulates the pathways of coupled protein folding and binding. Journal of the American Chemical Society, 136(3), 822-825. https://doi.org/10.1021/ja4086726