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

@article{citeulike:2368927, 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. 10.1073/pnas.0709741105}, author = {Li, Xiang-Dong and Jung, Hyun S. and Wang, Qizhi and Ikebe, Reiko and Craig, Roger and Ikebe, Mitsuo }, citeulike-article-id = {2368927}, doi = {10.1073/pnas.0709741105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {experiment, mutant, myosin, regulation}, month = {January}, number = {4}, pages = {1140--1145}, posted-at = {2008-02-13 08:36:37}, priority = {2}, title = {The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va}, url = {http://dx.doi.org/10.1073/pnas.0709741105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2368927 L3 - citeulike-article-id:2368927 TI - The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va JF - Proceedings of the National Academy of Sciences VL - 105 IS - 4 SP - 1140 EP - 1145 N2 - 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. 10.1073/pnas.0709741105 KW - experiment KW - mutant KW - myosin KW - regulation AU - Li, Xiang-Dong AU - Jung, Hyun AU - Wang, Qizhi AU - Ikebe, Reiko AU - Craig, Roger AU - Ikebe, Mitsuo PY - 2008/01/29/ UR - http://dx.doi.org/10.1073/pnas.0709741105 ER -