Temperature-enhanced association of proteins due to electrostatic interaction

A coarse-grained simulation of actin-myosin binding

Kei Ichi Okazaki, Takato Sato, Mitsunori Takano

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Association of protein molecules constitutes the basis for the interaction network in a cell. Despite its fundamental importance, the thermodynamic aspect of protein-protein binding, particularly the issues relating to the entropy change upon binding, remains elusive. The binding of actin and myosin, which are vital proteins in motility, is a typical example, in which two different binding mechanisms have been argued: the binding affinity increases with increasing temperature and with decreasing salt-concentration, indicating the entropy-driven binding and the enthalpy-driven binding, respectively. How can these thermodynamically different binding mechanisms coexist? To address this question, which is of general importance in understanding protein-protein bindings, we conducted an in silico titration of the actin-myosin system by molecular dynamics simulation using a residue-level coarse-grained model, with particular focus on the role of the electrostatic interaction. We found a good agreement between in silico and in vitro experiments on the salt-concentration dependence and the temperature dependence of the binding affinity. We then figured out how the two binding mechanisms can coexist: the enthalpy (due to electrostatic interaction between actin and myosin) provides the basal binding affinity, and the entropy (due to the orientational disorder of water molecules) enhances it at higher temperatures. In addition, we analyzed the actin-myosin complex structures observed during the simulation and obtained a variety of weak-binding complex structures, among which were found an unusual binding mode suggested by an earlier experiment and precursor structures of the strong-binding complex proposed by electron microscopy. These results collectively indicate the potential capability of a residue-level coarse-grained model to simulate the association-dissociation dynamics (particularly for transient weak-bindings) exhibited by larger and more complicated systems, as in a cell.

    Original languageEnglish
    Pages (from-to)8918-8925
    Number of pages8
    JournalJournal of the American Chemical Society
    Volume134
    Issue number21
    DOIs
    Publication statusPublished - 2012 May 30

    Fingerprint

    Myosins
    Coulomb interactions
    Static Electricity
    Actins
    Entropy
    Association reactions
    Proteins
    Temperature
    Protein Binding
    Computer Simulation
    Enthalpy
    Molecular Motor Proteins
    Salts
    Molecules
    Molecular Dynamics Simulation
    Titration
    Thermodynamics
    Electron microscopy
    Molecular dynamics
    Electron Microscopy

    ASJC Scopus subject areas

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

    Cite this

    Temperature-enhanced association of proteins due to electrostatic interaction : A coarse-grained simulation of actin-myosin binding. / Okazaki, Kei Ichi; Sato, Takato; Takano, Mitsunori.

    In: Journal of the American Chemical Society, Vol. 134, No. 21, 30.05.2012, p. 8918-8925.

    Research output: Contribution to journalArticle

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