Actin-Myosin Interaction: Structure, Function and Drug Discovery
AbstractActin-myosin interactions play crucial roles in the generation of cellular force and movement. The molecular mechanism involves structural transitions at the interface between actin and myosin’s catalytic domain, and within myosin’s light chain domain, which contains binding sites for essential (ELC) and regulatory light chains (RLC). High-resolution crystal structures of isolated actin and myosin, along with cryo-electron micrographs of actin-myosin complexes, have been used to construct detailed structural models for actin-myosin interactions. However, these methods are limited by disorder, particularly within the light chain domain, and they do not capture the dynamics within this complex under physiological conditions in solution. Here we highlight the contributions of site-directed fluorescent probes and time-resolved fluorescence resonance energy transfer (TR-FRET) in understanding the structural dynamics of the actin-myosin complex in solution. A donor fluorescent probe on actin and an acceptor fluorescent probe on myosin, together with high performance TR-FRET, directly resolves structural states in the bound actin-myosin complex during its interaction with adenosine triphosphate (ATP). Results from these studies have profound implications for understanding the contractile function of actomyosin and establish the feasibility for the discovery of allosteric modulators of the actin-myosin interaction, with the ultimate goal of developing therapies for muscle disorders. View Full-Text
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Guhathakurta, P.; Prochniewicz, E.; Thomas, D.D. Actin-Myosin Interaction: Structure, Function and Drug Discovery. Int. J. Mol. Sci. 2018, 19, 2628.
Guhathakurta P, Prochniewicz E, Thomas DD. Actin-Myosin Interaction: Structure, Function and Drug Discovery. International Journal of Molecular Sciences. 2018; 19(9):2628.Chicago/Turabian Style
Guhathakurta, Piyali; Prochniewicz, Ewa; Thomas, David D. 2018. "Actin-Myosin Interaction: Structure, Function and Drug Discovery." Int. J. Mol. Sci. 19, no. 9: 2628.
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