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

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)822-825
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number3
DOIs
StatePublished - Jan 22 2014
Externally publishedYes

Fingerprint

Protein folding
Protein Folding
Protein Binding
Ligands
Proteins
Ribonuclease P
Bacilli
Bacillus subtilis
Fluxes

ASJC Scopus subject areas

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

Cite this

Daniels, K. G., Tonthat, N. K., McClure, D. R., Chang, Y. C., Liu, X., Schumacher, M. A., ... 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

Ligand concentration regulates the pathways of coupled protein folding and binding. / Daniels, Kyle G.; Tonthat, Nam K.; McClure, David R.; Chang, Yu Chu; Liu, Xin; Schumacher, Maria A.; Fierke, Carol A.; Schmidler, Scott C.; Oas, Terrence G.

In: Journal of the American Chemical Society, Vol. 136, No. 3, 22.01.2014, p. 822-825.

Research output: Contribution to journalArticle

Daniels, KG, Tonthat, NK, McClure, DR, Chang, YC, Liu, X, Schumacher, MA, Fierke, CA, Schmidler, SC & Oas, TG 2014, 'Ligand concentration regulates the pathways of coupled protein folding and binding', Journal of the American Chemical Society, vol. 136, no. 3, pp. 822-825. https://doi.org/10.1021/ja4086726
Daniels, Kyle G. ; Tonthat, Nam K. ; McClure, David R. ; Chang, Yu Chu ; Liu, Xin ; Schumacher, Maria A. ; Fierke, Carol A. ; Schmidler, Scott C. ; Oas, Terrence G. / Ligand concentration regulates the pathways of coupled protein folding and binding. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 3. pp. 822-825.
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