It is unclear whether the reverse-direction myosin (myosin VI) functions as a monomer or dimer in cellsand how it generates large movements on actin. We deleted a stable, single-α-helix (SAH) domain thathas been proposed to function as part of a lever arm to amplify movements without impact on invitro movement or invivo functions. A myosin VI construct that used this SAH domain as part of its lever arm was able to take large steps invitro but did not rescue invivo functions. It was necessary for myosin VI to internally dimerize, triggering unfolding of a three-helix bundle and calmodulin binding in order to step normally invitro and rescue endocytosis and Golgi morphology in myosin VI-null fibroblasts. A model for myosin VI emerges in which cargo binding triggers dimerization and unfolds the three-helix bundle to create a lever arm essential for invivo functions.
Mukherjea, M., Ali, M. Y., Kikuti, C., Safer, D., Yang, Z., Sirkia, H., … Sweeney, H. L. (2014). Myosin VI Must Dimerize and Deploy Its Unusual Lever Arm in Order to Perform Its Cellular Roles. Cell Reports, 8(5), 1522-1532,. https://doi.org/10.1016/j.celrep.2014.07.041