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Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1140-5. doi: 10.1073/pnas.0709741105. Epub 2008 Jan 23.

The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va.

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1
Departments of Physiology and Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3658.

Abstract

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.

PMID:
18216256
PMCID:
PMC2234105
DOI:
10.1073/pnas.0709741105
[Indexed for MEDLINE]
Free PMC Article
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