2ld3 | pdb_00002ld3
Solution structure of myosin VI lever arm extension
Structural highlights
DiseaseMYO6_MOUSE Note=Defects in Myo6 are the cause of Snell's waltzer, a condition characterized by circling, head-tossing, deafness and hyperactivity. FunctionMYO6_MOUSE Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells. Publication Abstract from PubMedMyosin VI, the only known minus-ended actin filament-dependent motor, plays diverse cellular roles both as a processive motor and as a mechanical anchor. Although myosin VI has a short lever arm containing only one "IQ-motif" and a unique insertion for CaM binding, the motor walks with large and variable step sizes of approximately 30-36 nm. Here, we show that the previously predicted coiled-coil domain immediately following the IQ-motifs (referred to as the lever arm extension (LAE)) adopts a stable monomeric, three-helix bundle fold in solution. Importantly, the LAE can undergo reversible, lipid membrane-dependent conformational changes. Upon exposure to lipid membranes, the LAE adopts a partially extended rod shape, and the removal of lipids from the LAE converts it back into the compact helix bundle structure. Molecular dynamics simulations indicate that lipid membrane binding may initiate unfolding and thereby trigger the LAE expansion. This reversible, lipid membrane-dependent expansion of the LAE provides a mechanistic base for myosin VI to walk with large and variable step sizes. Membrane-induced lever arm expansion allows myosin VI to walk with large and variable step sizes.,Yu C, Lou J, Wu J, Pan L, Feng W, Zhang M J Biol Chem. 2012 Oct 12;287(42):35021-35035. doi: 10.1074/jbc.M111.328781. Epub , 2012 Aug 30. PMID:22936804[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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