Force production of myosin 18 and its molecular sociology with myosin 2

The cytoskeleton is a complex protein web organised through the cell to provide structure and cell shape dynamics. One critical and often overlooked component is Myo18, which is part of the myosin superfamily of motor proteins. By interacting with actin, myosins canonically produce force through a series of conformational changes driven by the hydrolysis of ATP. However, Myo18 appears not to cycle through the set of conformations found for other myosins due to its divergent sequence. It is therefore hypothesised to act as an actin cross-linker rather than actively producing force. Another myosin family, Myo2, is the most prominent force producing component in the muscle sarcomere and in stress fibres which drive cell migration. Myo2 performs its role by forming filaments through a coiled coil domain creating a structure with multiple force producing heads ready to bind and move along actin. The coiled coil of Myo18 allows recruitment into Myo2 filaments within these niches but its role is obscure given its divergent behaviour. The sociology between these two myosin families, that is the specific interactions of different partners in space and time, is interesting given the complementary features of these two protein families. This study aims to structurally characterise Myo18 in different nucleotide states on and off actin to gain insights into the evolution and function of its cryptic cycle. Furthermore, this work will assess through structural characterisation how Myo18 and Myo2 directly interact through their coiled coil domains. This association will then be analysed through biophysical studies exploring how Myo18 alters force production and function by intercalating into Myo2 filaments.