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Myosin
Myosins constitute a large multigene family of actin-based molecular motors in eukaryotes. Family members are widely expressed and tightly integrated in cellular networks of interlinked biochemical pathways where they function as integrators between signaling and the dynamics of cytoskeletal mechanics. As highly allosteric enzymes, the stringent regulation is a prerequisite for myosin’s function in active transport processes, cytoplasmic contractility, and mechanosensing in both physiological and pathological processes. The diversity of cellular functions in which myosins are involved is attributed to characteristic structural, enzymatic and regulatory properties of individual members of the myosin superfamily. At the level of primary sequence, a myosin heavy chain consists of a motor domain, a neck domain and a tail domain. The myosin motor domain harbors both a prototypic ATP binding site as well as a binding region for filamentous actin and allosterically links a repeated cycle of ATPase activity to its translocation on actin.
The primary regulation of this myosin is via phosphorylation of its RLC. In the absence of phosphorylation of nonmuscle myosin-2b is inactive and adopts a monomeric conformation where the two heads make an asymmetric interaction and where the tail folds in hairpins at two locations to give rise to a compact conformation lacking actin-activated ATPase activity and the ability to form filaments. Phosphorylation of Ser-19 on the RLC disrupts this conformation, allowing the myosin to assemble into bipolar filaments where the myosin motor domains can interact productively with actin that result in stimulation of the ATPase activity and translocation of actin filaments. Several kinases which are targets of different signal transduction pathways can affect this phosphorylation including Rho-associated protein kinase and MLCK, which is Ca2+-calmodulin dependent. The RLC can also be phosphorylated at Thr-18 which is further stimulatory and at Ser-1/2 and Thr-9 which are inhibitory to a certain extent. The activity of individual myosin-2b filaments can be modulated by co-polymerization with nonmuscle myosins-2a and -2c or with the pseudoenzyme myosin-18a.
References
1.Heissler SM,et al. J Mol Biol. 2016;428(9 Pt B):1927–1946.
The primary regulation of this myosin is via phosphorylation of its RLC. In the absence of phosphorylation of nonmuscle myosin-2b is inactive and adopts a monomeric conformation where the two heads make an asymmetric interaction and where the tail folds in hairpins at two locations to give rise to a compact conformation lacking actin-activated ATPase activity and the ability to form filaments. Phosphorylation of Ser-19 on the RLC disrupts this conformation, allowing the myosin to assemble into bipolar filaments where the myosin motor domains can interact productively with actin that result in stimulation of the ATPase activity and translocation of actin filaments. Several kinases which are targets of different signal transduction pathways can affect this phosphorylation including Rho-associated protein kinase and MLCK, which is Ca2+-calmodulin dependent. The RLC can also be phosphorylated at Thr-18 which is further stimulatory and at Ser-1/2 and Thr-9 which are inhibitory to a certain extent. The activity of individual myosin-2b filaments can be modulated by co-polymerization with nonmuscle myosins-2a and -2c or with the pseudoenzyme myosin-18a.
References
1.Heissler SM,et al. J Mol Biol. 2016;428(9 Pt B):1927–1946.
