PubMed ID

18216256

UMMS Affiliation

Departments of Physiology; Cell Biology

Date

1-25-2008

Document Type

Article

Subjects

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

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: 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

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Link to Article in PubMed