Amide temperature coefficients in characterizing the allosteric effects of ligand binding on local stability in proteins

Biochem Biophys Res Commun. 2020 Apr 9;524(3):677-682. doi: 10.1016/j.bbrc.2020.01.144. Epub 2020 Feb 4.

Abstract

Proteins can stabilize upon binding a ligand. Due to allosteric effects, the changes in stability can occur at regions far from the protein:ligand interface. Efficient methods to measure the changes in local stability upon ligand binding will be useful to understand allostery and may be helpful in protein engineering. In this work, we suggest the measurement of backbone amide temperature coefficients to probe the effect of ligand binding on the local stability of β-sheet rich proteins. The method was applied for two protein:ligand complexes with different binding affinities. The protein includes a beta-sheet network connected by hydrogen bonds. The measured temperature coefficient data captured the stabilizing effect of ligand binding, which propagated across the beta-sheet network of the protein. Intriguingly, the impact on the local and global stability of the protein was proportional to the strength of protein:ligand interaction.

Keywords: Allostery; Amide temperature coefficient; NMR; Protein:ligand complex; Proteins; SUMO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Amides / chemistry*
  • Amino Acid Motifs
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Protein Binding
  • Protein Stability
  • SUMO-1 Protein / chemistry
  • SUMO-1 Protein / metabolism
  • Temperature*

Substances

  • Amides
  • Ligands
  • SUMO-1 Protein
  • SUMO1 protein, human