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

作者：Li Xiang dong^*; Jung Hyun Suk; Wang Qizhi; Ikebe Reiko; Craig Roger; Ikebe Mitsuo

来源：Proceedings of the National Academy of Sciences, 2008, 105(4): 1140-1145.

DOI：10.1073/pnas.0709741105

• actin
• trafficking
• molecular motor
• lever arm
• regulation

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 ATIP hydrolysis cycle, thus inhibiting the chemical cycle of the motor domain.

• 出版日期2008-1-29