Title: Understanding the Stability and Flexibility of the Unusually Long Single Alpha-Helical Tail Domain of Myosin VI using Molecular Dynamics Simulations

Abstract:
Myosin VI is the only known minus-end directed actin-based motor which functions in a variety of cellular processes including endocytosis, protein secretion and maintenance of Golgi-morphology. Myosin VI takes ~ 36 nm steps along an actin filament despite a short lever arm (~ 12 nm). This is made possible in part by a highly charged segment of the myosin VI helical-tail (medial tail) which is a single stable alpha-helix in solution without tertiary contacts. Such a structural motif is rarely seen in proteins wherein alpha-helices embedded within the protein structure are regularly stabilized by tertiary interactions. The medial-tail must be sufficiently rigid to extend the myosin VI step while being flexible to allow a potential regulatory interaction between the myosin VI catalytic head and the cargo binding domain. I will present studies of the stability and flexibility of the medial-tail of myosin VI using molecular dynamics simulations.