Ligand concentration regulates the pathways of coupled protein folding and binding.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Daniels, KG; Tonthat, NK; McClure, DR; Chang, Y-C; Liu, X; Schumacher, MA; Fierke, CA; Schmidler, SC; Oas, TG

Published Date

  • January 22, 2014

Published In

Volume / Issue

  • 136 / 3

Start / End Page

  • 822 - 825

PubMed ID

  • 24364358

Pubmed Central ID

  • PMC3977005

Electronic International Standard Serial Number (EISSN)

  • 1520-5126

Digital Object Identifier (DOI)

  • 10.1021/ja4086726


  • eng

Conference Location

  • United States