By visualization at high resolution of the myosin states that correspond to several steps of their motor cycle using Xray crystallography, the Structural Motility team has an international reputation for its contributions in the understanding of the motor mechanism of myosin motors. We also identify the structural determinants specific of a reverse motor, myosin VI, that produces force in the opposite direction than all other characterized myosin motors. These results have been published in seven major publications in the journals Nature, Cell, Mol Cell and Embo Journal. The results on myosin VI are particularly interesting since the structure of the four first states of its motor cycle have been solved (see Figure). This corresponds to the biggest contribution for the same motor obtained to date. This allowed us to deepen our understanding of how force is produced by myosins in general but also to describe the special adaptations of the motor necessary to walk in opposite direction with very large steps despite a short lever arm. One must note that a novel structural state has been characterized who will deliver unvaluable information to understand how actin inititates the early stages of the powerstroke. The current projects of the team involve describing the structural features that allow different motors of the superfamily to be adapted to different motility functions. We will study Myosin VI for example to understand how partners can regulate the motor for anchoring or transport functions. With Myosin X, we will also study how this motor can promote the assembly of filopodia and which roles it plays in the maintenance of this actinrich protrusion. We will address the fundamental question of how an individual myosin molecule identifies and walks along the correct actin filament. We will take as a model myosin X, which walks along two filaments instead of one, allowing for the identification of the correct path to filopodial tips (see Figure).
Scientific keywords: force production, Molecular motors, myosins, structural biology
Technics Used in the Lab: X-ray crystallography, SAXS, biophysical characterization of proteins and protein interactions