Background: Myosin-19 is strongly associated with mitochondria and plays a role in the transport of mitochondria. Results: The light chains of myosin-19 are the regulatory light chains of myosin-2. ADP release is rate-limiting for acto-Myo19 ATPase and ADP strongly inhibits myosin-19 motor function. Conclusion: Myosin-19 is a plus-end-directed, high-duty ratio molecular motor. Significance: Myosin-19 functions as a molecular motor.

Background: Myosin 5a ATPase activity is regulated by calcium. Results: The ATPase of the truncated myosin 5a having the motor domain and the first IQ motif is inhibited by its tail in a calcium-dependent manner. Conclusion:The calmodulin in the first IQ motif of myosin 5a is responsible for calcium-dependent regulation. Significance: This presents a new paradigm for calcium regulation of unconventional myosins.

The tail-inhibition model is generally accepted for the regulation of myosin-5a motor function. Inhibited myosin-5a is in a folded conformation in which its globular tail domain (GTD) interacts with its head and inhibits its motor function, and high Ca2+ or cargo binding may reduce the interaction between the GTD and the head of myosin-5a, thus activating motor activity. Although it is well established that myosin-5a motor function is regulated by Ca2+, little is known about the effects of cargo binding. We previously reported that melanophilin (Mlph), a myosin-5a cargo-binding protein, is capable of activating myosin-5a motor function. Here, we report that Mlph-GTBDP, a 26 amino-acid-long peptide of Mlph, is sufficient for activating myosin-5a motor function. We demonstrate that Mlph-GTBDP abolishes the interaction between the head and GTD of myosin-5a, thereby inducing a folded-to-extended conformation transition for myosin-5a and activating its motor function. Mutagenesis of the GTD shows that the GTD uses two distinct, non-overlapping regions to interact with Mlph-GTBDP and the head of myosin-5a. We propose that the GTD is an allosteric protein and that Mlph allosterically inhibits the interaction between the GTD and head of myosin-5a, thereby activating myosin-5a motor function.