Li, X.D. et al. The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va. Proc. Natl. Acad. Sci. USA 105, 1140-1145

Departments of Physiology and Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2008; 105(4):1140-5. DOI: 10.1073/pnas.0709741105
Source: PubMed


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.

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    • "Sequence alignment with mouse myosin Va and a further literature survey indicated that the corresponding amino acids (Lys1706 and Lys1779) from myosin Va are those that mediate the tail and head interaction in this myosin (Li et al., 2008). It has been suggested that tail folding and interaction with the head is a regulatory mechanism inhibiting myosin ATPase activity and the function of myosin Va (Li et al., 2008). This suggests that myosin XIK can fold and form a head–tail interaction. "
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    • "The end of this first coiled-coil region is critical in stabilizing the folded triangular structure of Myo5a and prevents the conformational changes of the motor domain during the ATP turnover cycle, consequently inhibiting the actin-activated ATPase activity of the motor domain (Li et al., 2006, 2008; Sato et al., 2007). Very recently, Li et al. (2008) identified a conserved acidic residue (D136) in the motor domain and two conserved basic residues (K1706 and K1779) in the GTD as critical residues involved in this inhibition of Myo5a. "
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