Departments of Physiology; Cell Biology
Adenosine Triphosphatases; Alanine; Amino Acid Substitution; Animals; *Aspartic Acid; Chickens; Conserved Sequence; Lysine; Mice; Models, Molecular; Mutagenesis, Site-Directed; Myosin Heavy Chains; inhibitors; Myosin Type V; Protein Structure, Tertiary
Life Sciences | Medicine and Health Sciences
Myosin Va is a well known processive motor involved in transport of organelles. A tail-inhibition model is generally accepted for the regulation of myosin Va: inhibited myosin Va is in a folded conformation such that the tail domain interacts with and inhibits myosin Va motor activity. Recent studies indicate that it is the C-terminal globular tail domain (GTD) that directly inhibits the motor activity of myosin Va. In the present study, we identified a conserved acidic residue in the motor domain (Asp-136) and two conserved basic residues in the GTD (Lys-1706 and Lys-1779) as critical residues for this regulation. Alanine mutations of these conserved charged residues not only abolished the inhibition of motor activity by the GTD but also prevented myosin Va from forming a folded conformation. We propose that Asp-136 forms ionic interactions with Lys-1706 and Lys-1779. This assignment locates the GTD-binding site in a pocket of the motor domain, formed by the N-terminal domain, converter, and the calmodulin in the first IQ motif. We propose that binding of the GTD to the motor domain prevents the movement of the converter/lever arm during ATP hydrolysis cycle, thus inhibiting the chemical cycle of the motor domain.
DOI of Published Version
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1140-5. Epub 2008 Jan 23. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Li X, Jung H, Wang Q, Ikebe R, Craig RW, Ikebe M. (2008). The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va. Open Access Publications by UMMS Authors. https://doi.org/10.1073/pnas.0709741105. Retrieved from https://escholarship.umassmed.edu/oapubs/1971