Protein conformational dynamics dictate the binding affinity for a ligand

• Published in: Nature communications 2014-04, Vol.5 (1), p.3724-3724, Article 3724
• Main Authors: Seo, Moon-Hyeong, Park, Jeongbin, Kim, Eunkyung, Hohng, Sungchul, Kim, Hak-Sung
• Format: Article
• Language: English
• Subjects: 631/45/535; 631/57/2272; 96/33; Humanities and Social Sciences; Labeling; Ligands; Maltose-Binding Proteins - chemistry; Models, Molecular; multidisciplinary; Mutation; Polyethylene glycol; Protein Conformation; Proteins; Science; Science (multidisciplinary); Signal transduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4724

Interactions between a protein and a ligand are essential to all biological processes. Binding and dissociation are the two fundamental steps of ligand–protein interactions, and determine the binding affinity. Intrinsic conformational dynamics of proteins have been suggested to play crucial roles in ligand binding and dissociation. Here, we demonstrate how protein dynamics dictate the binding and dissociation of a ligand through a single-molecule kinetic analysis for a series of maltose-binding protein mutants that have different intrinsic conformational dynamics and dissociation constants for maltose. Our results provide direct evidence that the ligand dissociation is determined by the intrinsic opening rate of the protein. The binding affinity of a protein for its ligand is governed by the rates of ligand association and dissociation. Here the authors show that intrinsic conformational dynamics of maltose binding protein dictate the ligand dissociation rate, and hence the affinity of the protein for maltose.