4JG4

Ligand concentration regulates the pathways of coupled protein folding and binding

Summary for 4JG4

• Entry DOI: 10.2210/pdb4jg4/pdb
• Descriptor: Ribonuclease P protein component, PYROPHOSPHATE (3 entities in total)
• Functional Keywords: rna-binding, endonuclease, hydrolase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 1
• Total formula weight: 14675.44

Authors

Tonthat, N.K. (deposition date: 2013-02-28, release date: 2014-01-22, Last modification date: 2024-02-28)

Primary citation

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.
Ligand concentration regulates the pathways of coupled protein folding and binding.
J.Am.Chem.Soc., 136:822-825, 2014

PubMed 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.

PubMed: 24364358
DOI: 10.1021/ja4086726

Experimental method

X-RAY DIFFRACTION (2.296 Å)